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Clinical Trial Results:
Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)

Summary
EudraCT number	2004-003635-31
Trial protocol	AT BE GB CZ IT DE ES SE HU PT
Global end of trial date	18 Nov 2015

Results information
Results version number	v1(current)
This version publication date	18 Jun 2016
First version publication date	18 Jun 2016
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

IM103-008

ISRCTN number

US NCT number

NCT00256750

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussee de la Hulpe 185, Brussels, Belgium, 1170

Public contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, clinical.trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, clinical.trials@bms.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

18 Nov 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Nov 2015

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial was to evaluate the effect of belatacept to provide protection from organ rejection following kidney transplantation while avoiding some of the toxic effects of standard immunosuppressive medications such as kidney damage. Effects on kidney function and subject survival as well as drug safety were also studied.

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Jan 2006

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

24 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 51

Country: Number of subjects enrolled

Austria: 8

Country: Number of subjects enrolled

Australia: 28

Country: Number of subjects enrolled

Belgium: 11

Country: Number of subjects enrolled

Brazil: 60

Country: Number of subjects enrolled

Canada: 35

Country: Number of subjects enrolled

Czech Republic: 6

Country: Number of subjects enrolled

France: 90

Country: Number of subjects enrolled

Germany: 4

Country: Number of subjects enrolled

Hungary: 2

Country: Number of subjects enrolled

India: 98

Country: Number of subjects enrolled

Israel: 3

Country: Number of subjects enrolled

Italy: 16

Country: Number of subjects enrolled

Mexico: 99

Country: Number of subjects enrolled

Poland: 6

Country: Number of subjects enrolled

South Africa: 6

Country: Number of subjects enrolled

Spain: 19

Country: Number of subjects enrolled

Sweden: 5

Country: Number of subjects enrolled

Switzerland: 3

Country: Number of subjects enrolled

Turkey: 2

Country: Number of subjects enrolled

United States: 186

Worldwide total number of subjects

738

EEA total number of subjects

167

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

694

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 34 centers in 21 countries.

Screening details

738 subjects enrolled, 686 subjects randomized. Reasons for non-randomization include 5 subjects withdrew consent, 1 subject lost to follow-up, 34 subjects no longer met study criteria, and 12 subjects for other non-listed reasons. 20 not transplanted; 10, 4, 6 in the CsA, Belatacept LI, Belatacept MI, respectively.

Period 1 title

Transplanted Pre-Treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Cyclosporine

Arm description

Cyclosporine (CsA): tablet, oral 1st month target: 150-300 nanogram/meter (ng/m) After 1st month target: 100-250 nanogram/milliliter (ng/mL), daily, 36 months (short term = ST), 100-250 ng/mL, daily, 24 months (long term = LT)

Arm type

Active comparator

Investigational medicinal product name

Cyclosporine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received cyclosporine 150-300 ng/mL and 100-250 ng/mL at Month 1 and after Month 1, respectively.

Belatacept LI

Arm description

Belatacept LI (less intensive): solution, intravenous (IV), 10 milligrams/kilogram (mg/kg): Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every (q) 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Belatacept MI

Arm description

Belatacept MI (more intensive): solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 milligrams/kilogram (mg/kg) every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Number of subjects in period 1 ^[1]	Cyclosporine	Belatacept LI	Belatacept MI
Started	221	226	219
Completed	215	226	219
Not completed	6	0	0
Adverse event, serious fatal	1	-	-
Consent withdrawn by subject	3	-	-
Not specified	2	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The number of subjects reported in the baseline period are different from the worldwide number enrolled in the trial, as out of 738 subjects enrolled only 666 were transplanted, rest 52 subjects were not randomised and 20 were not transplanted.

Period 2 title

Post-Transplant Treated (12 months)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Cyclosporine

Arm description

Arm type

Active comparator

Investigational medicinal product name

Cyclosporine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received cyclosporine 150-300 ng/mL and 100-250 ng/mL at Month 1 and after Month 1, respectively.

Belatacept LI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Belatacept MI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Number of subjects in period 2	Cyclosporine	Belatacept LI	Belatacept MI
Started	215	226	219
Completed	174	183	173
Not completed	41	43	46
Adverse event, serious fatal	3	2	4
Consent withdrawn by subject	-	3	5
Adverse event, non-fatal	20	12	8
Not specified	5	4	2
Lost to follow-up	1	-	-
Protocol deviation	2	-	-
Lack of efficacy	10	22	27

Period 3 title

Post-Transplant Treated (24 months)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Cyclosporine

Arm description

Arm type

Active comparator

Investigational medicinal product name

Cyclosporine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received cyclosporine 150-300 ng/mL and 100-250 ng/mL at Month 1 and after Month 1, respectively.

Belatacept LI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Belatacept MI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Number of subjects in period 3	Cyclosporine	Belatacept LI	Belatacept MI
Started	174	183	173
Completed	153	176	164
Not completed	21	7	9
Adverse event, serious fatal	3	-	-
Consent withdrawn by subject	5	1	-
Adverse event, non-fatal	7	3	6
Not specified	2	-	1
Lack of efficacy	4	3	2

Period 4 title

Post-Transplant Treated (36 months)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Cyclosporine

Arm description

Arm type

Active comparator

Investigational medicinal product name

Cyclosporine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received cyclosporine 150-300 ng/mL and 100-250 ng/mL at Month 1 and after Month 1, respectively.

Belatacept LI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Belatacept MI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Number of subjects in period 4	Cyclosporine	Belatacept LI	Belatacept MI
Started	153	176	164
Completed	143	170	158
Not completed	10	6	6
Adverse event, serious fatal	-	2	1
Consent withdrawn by subject	1	-	1
Adverse event, non-fatal	5	1	2
Not specified	-	1	1
Subject no longer meets study criteria	-	-	1
Lack of efficacy	4	1	-
Protocol deviation	-	1	-

Period 5 title

Long Term Extension (LTE; 84 months)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Are arms mutually exclusive

Yes

Cyclosporine

Arm description

Arm type

Active comparator

Investigational medicinal product name

Cyclosporine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received cyclosporine 150-300 ng/mL and 100-250 ng/mL at Month 1 and after Month 1, respectively.

Belatacept LI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Belatacept MI

Arm description

Arm type

Experimental

Investigational medicinal product name

Belatacept

Investigational medicinal product code

BMS-224818

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received belatacept 10 mg/kg intravenously and a maintenance dose of 5 mg/kg.

Number of subjects in period 5 ^[2]	Cyclosporine	Belatacept LI	Belatacept MI
Started	136	166	155
Completed	89	136	127
Not completed	47	30	28
Adverse event, serious fatal	9	4	4
Consent withdrawn by subject	5	4	1
Adverse event, non-fatal	13	11	14
Not specified	5	4	5
Administrative Reason By Sponsor	1	1	-
Pregnancy	-	1	2
Poor/Non-compliance	4	1	1
Lost to follow-up	4	1	1
Lack of efficacy	6	3	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The number of subjects starting the period was not consistent with the number completing the preceding period as some subjects discontinued and not opted to participate in long term period due to various reasons.

Baseline characteristics

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Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept LI

Reporting group description

Reporting group title

Belatacept MI

Reporting group description

Reporting group values	Cyclosporine	Belatacept LI	Belatacept MI	Total
Number of subjects	221	226	219	666
Age, Customized
Units: subjects
Between 18 and 45 years:	110	124	111	345
Between 46 and 65 years:	101	93	93	287
> 65 years:	10	9	15	34
Age Continuous
Units: years
arithmetic mean (standard deviation)	43.5 ± 14.3	42.6 ± 13.4	43.6 ± 14.6	-
Gender, Male/Female
Units: subjects
Female	56	80	68	204
Male	165	146	151	462
Previous Number of Transplant
Units: Subjects
0x	208	218	210	636
1x	9	5	5	19
2x	0	0	1	1
Missing	4	3	3	10

End points

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Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept LI

Reporting group description

Reporting group title

Belatacept MI

Reporting group description

Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept LI

Reporting group description

Reporting group title

Belatacept MI

Reporting group description

Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept LI

Reporting group description

Reporting group title

Belatacept MI

Reporting group description

Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept LI

Reporting group description

Reporting group title

Belatacept MI

Reporting group description

Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept LI

Reporting group description

Reporting group title

Belatacept MI

Reporting group description

Primary: Percent of Subjects Surviving with a Functioning Graft by Month 12

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End point title

Percent of Subjects Surviving with a Functioning Graft by Month 12

End point description

End point type

Primary

End point timeframe

Day 1 to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)	92.8 (89.3 to 96.2)	96.5 (94.1 to 98.9)	95.4 (92.7 to 98.2)

Subject and graft survival at Month 12

Statistical analysis description

A non-inferiority margin of 10% for the co-primary endpoint of subject and graft survival was used. Determination of a margin for non-inferiority based on 'preservation of benefit' is not feasible, given the low rate of subject death and/or graft loss in the first year post-transplantation, and the absence of published, adequately sized, parallel-group trials with which to assess the effect of CsA on subject death and/or graft loss in the setting of MMF/steroids/basiliximab.

Comparison groups

Cyclosporine v Belatacept MI

Number of subjects included in analysis

440

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Difference in percentage

Point estimate

2.7

Confidence interval

level

97.3%

sides

2-sided

lower limit

-2.5

upper limit

8.1

Subject and graft survival at Month 12

Statistical analysis description

Comparison groups

Cyclosporine v Belatacept LI

Number of subjects included in analysis

447

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Difference in percentage

Point estimate

3.7

Confidence interval

level

97.3%

sides

2-sided

lower limit

-1.1

upper limit

Primary: Percent of Subjects with a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or with a Decrease in mGFR Greater Than or Equal to 10 mL/min/1.73m^2 From Month 3 to Month 12

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End point title

Percent of Subjects with a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or with a Decrease in mGFR Greater Than or Equal to 10 mL/min/1.73m^2 From Month 3 to Month 12

End point description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 mg/dL. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in SCr of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Primary

End point timeframe

Month 12; Month 3 to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	213	214	209
Units: percentage of subjects
number (confidence interval 95%)	77.9 (72.4 to 83.5)	54.2 (47.5 to 60.9)	55 (48.3 to 61.8)

Difference between belatacept & CsA renal function

Comparison groups

Cyclosporine v Belatacept LI

Number of subjects included in analysis

427

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0 ^[1]

Method

Chi-squared corrected

Parameter type

Difference in percentage

Point estimate

-23.7

Confidence interval

level

97.3%

sides

2-sided

lower limit

-33.3

upper limit

-13.7

Notes
[1] - A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine

Difference between belatacept & CsA renal function

Comparison groups

Cyclosporine v Belatacept MI

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0 ^[2]

Method

Chi-squared corrected

Parameter type

Difference in percentage

Point estimate

-22.9

Confidence interval

level

97.3%

sides

2-sided

lower limit

-32.6

upper limit

-12.9

Notes
[2] - A continuity-corrected Chi-square test at significance level 0.027 was performed for the difference between the belatacept regimen and cyclosporine

Primary: Percent of Subjects Experiencing Acute Rejection (AR) Post-transplant by Month 12

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End point title

Percent of Subjects Experiencing Acute Rejection (AR) Post-transplant by Month 12

End point description

Acute rejection was defined as a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence was defined if either a or b was satisfied: a: an unexplained rise of serum creatinine >=25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology: an international standardized histopathological classification. AR was defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each subject was counted. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Primary

End point timeframe

Day 1 to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)	7.2 (3.8 to 10.7)	17.3 (12.3 to 22.2)	21.9 (16.4 to 27.4)

Acute Rejection (AR) Post-transplant by Month 12

Statistical analysis description

A 20% margin for non-inferiority was used and provides 99% power to ascertain that the upper bound of the 97.3% 2-sided confidence intervals for the absolute difference between each belatacept regimen and cyclosporine, assuming the true acute rejection rate by 12 months is 15% for all three regimens

Comparison groups

Cyclosporine v Belatacept LI

Number of subjects included in analysis

447

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

97.3%

sides

2-sided

lower limit

3.3

upper limit

17.1

Acute Rejection (AR) Post-transplant by Month 12

Statistical analysis description

Comparison groups

Belatacept MI v Cyclosporine

Number of subjects included in analysis

440

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Difference in percentage

Point estimate

14.7

Confidence interval

level

97.3%

sides

2-sided

lower limit

7.5

upper limit

22.2

Secondary: Mean Value of the Measured Glomerular Filtration Rate (mGFR)

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End point title

Mean Value of the Measured Glomerular Filtration Rate (mGFR)

End point description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Months 3, 12, 24

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	201	215	209
Units: mL/min/1.73m^2
arithmetic mean (standard deviation)
Month 3 (n=201, 215, 209)	51.9 ± 21.09	61.7 ± 25.43	59.9 ± 28.47
Month 12 (n=199, 206, 200)	50.4 ± 18.71	63.4 ± 27.66	65 ± 30.02
Month 24 (n=185, 199, 192)	50.5 ± 20.52	67.9 ± 29.9	65 ± 27.21

No statistical analyses for this end point

Secondary: Percent of Subjects with Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

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End point title

Percent of Subjects with Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

End point description

Prevalence of CAN = if subject met any of the following conditions: a: CAN observed in a biopsy either prior to 12 months (including baseline biopsy) or first post 12 months biopsy; b: subject had graft loss during the first year post transplant; c: no biopsy was available post 12 months and CAN not observed in biopsies prior to 12 months, but the measured GFR from Month 3 to Month 12 decreased at least 10 mL/min/1.73m^2; d: no biopsy available either prior to or post 12 months, and the measured GFR (incorporated missing data imputation) from Month 3 to Month 12 decreased at least 10 mL/min/1.73m^2. CAN = All allograft biopsies evaluated for presence and severity of CAN by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Onset of CAN determined by the biopsy date when it was observed. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	219	226	219
Units: percentage of subjects
number (confidence interval 95%)	32.4 (26.2 to 38.6)	23.9 (18.3 to 29.5)	18.3 (13.1 to 23.4)

No statistical analyses for this end point

Secondary: Number of Subjects With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

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End point title

Number of Subjects With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

End point description

Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. All randomised and transplanted subjects from the original intent-to-treat (ITT) population who continued on assigned therapy into the long-term extension phase (ITT-LTE).

End point type

Secondary

End point timeframe

Randomisation to Month 84

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	136	166	155
Units: subjects
number (not applicable)
Deaths	9	7	7
SAEs	107	113	117
Discontinued due to SAEs	5	8	6
Discontinued due to AEs	12	11	14

No statistical analyses for this end point

Secondary: Number of Subjects with Adverse Events of Special Interest by Month 84

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End point title

Number of Subjects with Adverse Events of Special Interest by Month 84

End point description

Prospectively identified events of special interest which were a subset of all AEs, and were either SAEs or non-serious AEs, included the following categories: Serious Infections and Infestations, Thrombolic/embolic events, and Malignancy. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/ abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Time frame is from randomisation to the event date, or to the last dose date+56, or to Month 84 (Day 2548), whichever is the earliest. The analysis was performed in all randomised and transplanted subjects from the original intent-to-treat (ITT) population who continued on assigned therapy into the long-term extension phase (ITT-LTE).

End point type

Secondary

End point timeframe

Randomisation to Month 84

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	136	166	155
Units: subjects
number (not applicable)
Malignancies	22	16	20
Cytomegalovirus (CMV) Infections	19	24	20
BK Polyoma Virus Infections	6	10	15
Herpes Virus Infections	29	37	37
Fungal Infections	42	47	55
Tuberculosis Infections	2	1	5
Central Nervous System (CNS) Infections	0	0	1
Pulmonary edema or Chronic Heart Failure	12	4	5
Auto-immune Events	8	8	6

No statistical analyses for this end point

Secondary: Mean Blood Pressure at Month 84

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End point title

Mean Blood Pressure at Month 84

End point description

Blood pressure was measured in millimeters of mercury (mmHg). Blood pressure was measured soon after the subject arrived and sat quietly at rest for 10 minutes. 3 consecutive seated blood pressure readings were made at least 1 minute apart. The analysis was performed in all randomised and transplanted subjects from the original intent-to-treat (ITT) population who continued on assigned therapy into the long-term extension phase (ITT-LTE). Here, ‘Number of subjects Analysed’ signifies subjects evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Month 84

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	82	125	112
Units: mmHg
arithmetic mean (standard deviation)
Diastolic Blood Pressure	78.6 ± 11.03	75.8 ± 10.56	75.1 ± 10.15
Systolic Blood Pressure	129 ± 15.83	126.7 ± 18.17	126 ± 17.56

No statistical analyses for this end point

Secondary: Number of Subjects Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36

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End point title

Number of Subjects Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36

End point description

Upper limit of normal (ULN). Units per Liter (U/L). Cells per microliter (c/µL). Grams per deciliter (g/dL). Milligrams per deciliter (mg/dL).Cells per Liter (c/L). Milliequivalents/Liter (mEq/L). Hemoglobin (low): <8.0 g/dL; Platelet count: <50*10^9 c/L; Leukocytes: <2*10^3 c/µL; Alkaline phosphatase (ALP): >5.0*ULN U/L; Alanine aminotransferase (ALT): >5.0*ULN U/L; Asparate aminotransferase (AST): >5.0*ULN U/L; Bilirubin Total: >3.0*ULN mg/dL; Creatinine: >3.0*ULN mg/dL; Calcium Total: low if <7.0 mg/dL or high if >12.5 mg/dL; Bicarbonate: <11.0 mEq/L; Potassium serum: low if <3.0 mEq/L or high if >6.0 mEq/L; Magnesium serum: low is <0.8 mEq/L or high if >2.46 mEq/L; Sodium serum: low if <130.0 mEq/L or high if >155.0 mEq/L; Phosphorus inorganic: <2.0 mg/dL; Albumin: <2 g/dL; Uric acid: >10 mg/dL; Protein urine: >=3+. The analysis was performed in all randomised and transplanted subjects from the original intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Baseline to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: subjects
number (not applicable)
Hemoglobin, low (n=213, 226, 219)	26	25	27
Platelet count, low (n=213, 226, 218)	0	1	0
Leukocytes, low (n=213, 226, 219)	10	5	5
Alkaline phosphatase, high (n=214, 226, 219)	1	4	0
Alanine aminotransferase, high (n=214, 226, 219)	6	6	4
Aspartate aminotransferase, high (n=214, 226, 219)	2	3	3
Bilirubin total, high (n=214, 226, 219)	1	0	0
Calcium total, low (n=214, 226, 219)	7	8	4
Calcium total, high (n=214, 226, 219)	0	1	0
Bicarbonate, low (n=214, 226, 219)	1	0	0
Bicarbonate, high (n=214, 226, 219)	0	0	0
Potassium serum, low (n=213, 223, 219)	4	13	12
Potassium serum, high (n=213, 223, 219)	13	9	4
Magnessium serum, low (n=214, 225, 219)	1	2	1
Magnessium serum, high (n=214, 225, 219)	9	12	14
Sodium serum, low (n=214, 226, 219)	21	8	9
Sodium serum, high (n=214, 226, 219)	0	1	0
Phosphorus inorganic, low (n=213, 224, 219)	75	100	112
Albumin, low (n=214, 226, 219)	0	0	0
Uric acid, high (n=214, 226, 219)	42	7	11
Protein in urine, high (n=213, 224, 217)	33	30	36
Creatinine, high (n=213, 223, 219)	48	50	52

No statistical analyses for this end point

Secondary: Percent of Subjects With Development of Anti-Donor HLA Positive Antibodies by Month 84

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End point title

Percent of Subjects With Development of Anti-Donor HLA Positive Antibodies by Month 84

End point description

Only subjects who had non-missing test result for Class I or Class II anti-donor HLA antibodies were included in analysis and only subjects who had at least one non-NA test result or finding were counted. This was a cumulative summary (excluding baseline) and once a subject was positive, that subject remained positive for the later time point. Acute rejection (AR) defined: a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence defined: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. AR defined as allograft biopsies of Banff 97 classification Grade IA or greater (higher scores indicate more severe rejection). Evaluated by blinded central independent pathologist. The analysis was performed in ITT population.

End point type

Secondary

End point timeframe

Randomisation to Month 84

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	215	226	219
Units: percentage of subjects
number (confidence interval 95%)	11.6 (7.34 to 15.91)	3.1 (0.84 to 5.36)	1.4 (0.28 to 3.95)

No statistical analyses for this end point

Secondary: Mean Change of the Measured Glomerular Filtration Rate (mGFR) from Month 3 to Month 12 and from Month 3 to Month 24

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End point title

Mean Change of the Measured Glomerular Filtration Rate (mGFR) from Month 3 to Month 12 and from Month 3 to Month 24

End point description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. Missing mGRF assessments were imputed to assess renal function. The overall imputation strategy involved a primary imputation method (linear extrapolation and quartile method) followed by 2 secondary imputation methods (regression method and graded quartile method) to assess the robustness of conclusions obtained from the application of the primary imputation method. All imputation methods entailed replacing a missing value with a value drawn from a plausible distribution incorporating theoretical and observed aspects of the data. GFR was measured as mL/min/1.73 m^2. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 3 to Month 12; Month 3 to Month 24

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	195	206	200
Units: mL/min/1.73m^2
arithmetic mean (standard deviation)
Baseline (Month 3) to Month 12 (n=195, 206, 200)	-1.7 ± 21.58	1.2 ± 30.43	4.4 ± 31.1
Baseline (Month 3) to Month 24 (n=184, 199, 192)	-2 ± 25.23	5.3 ± 33.03	4.2 ± 30.96

No statistical analyses for this end point

Secondary: Percent of Subjects With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/min/1.73m^2 from Month 3 to Month 12

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End point title

Percent of Subjects With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/min/1.73m^2 from Month 3 to Month 12

End point description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A change in GFR of at least 10 mL/min/1.73 m^2 was used as the approximate change in serum creatinine (SCr) of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3. Month 3 = baseline. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 3 to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	213	214	209
Units: percentage of subjects
number (confidence interval 95%)	28.2 (22.1 to 34.2)	23.4 (17.7 to 29)	23 (17.3 to 28.7)

No statistical analyses for this end point

Secondary: Percent of Subjects with a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/min/1.73 m^2 at Month 12

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End point title

Percent of Subjects with a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/min/1.73 m^2 at Month 12

End point description

Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 milligrams per deciliter (mg/dL). The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	213	214	209
Units: percentage of subjects
number (confidence interval 95%)	67.6 (61.3 to 73.9)	43 (36.4 to 49.6)	43.5 (36.8 to 50.3)

No statistical analyses for this end point

Secondary: Mean Value of the Calculated Glomerular Filtration Rate (cGFR) with Imputation

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End point title

Mean Value of the Calculated Glomerular Filtration Rate (cGFR) with Imputation

End point description

Calculated glomerular filtration rate (cGFR) was used to assess renal function (as measured by the estimated creatinine clearance) using the following modification of diet in renal disease (MDRD) formula: MDRD: GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if subject is female] x [1.180 if subject is black] x [BUN]^(-0.170) x [Alb]^(+0.318); Age in years; Alb = Albumin in g/dL; SCr = Serum creatinine in mg/dL; BUN = Blood urea nitrogen in mg/dL; cGFR = mL/min/1.73m^2. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Months 6, 12, 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	199	201	201
Units: mL/min/1.73 m^2
arithmetic mean (standard deviation)
Month 6 (n=189, 185, 170)	48.8 ± 19.22	62.6 ± 20.41	62.4 ± 20.94
Month 12 (n=199, 200, 201)	50.1 ± 21.06	65.4 ± 22.94	65.2 ± 23.51
Month 24 (n=182, 201, 191)	47.9 ± 23	65.4 ± 25.22	65.5 ± 24.87
Month 36 (n=171, 190, 186)	44.4 ± 23.58	65.8 ± 27	65.2 ± 26.31

No statistical analyses for this end point

Secondary: Mean Change in Calculated Glomerular Filtration Rate (cGFR) from Month 6 to Month 12

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End point title

Mean Change in Calculated Glomerular Filtration Rate (cGFR) from Month 6 to Month 12

End point description

End point type

Secondary

End point timeframe

Month 6 to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	166	169	160
Units: mL/Min/1.73 m^2
arithmetic mean (standard deviation)	2.3 ± 10.09	4.7 ± 11.52	5.1 ± 11.37

No statistical analyses for this end point

Secondary: Percent of Subjects with Incidence of New Onset Diabetes Mellitus by Month 36

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End point title

Percent of Subjects with Incidence of New Onset Diabetes Mellitus by Month 36

End point description

The incidence of new onset diabetes mellitus defined as subjects who developed diabetes mellitus after randomization and transplantation. Subjects that did not have diabetes prior to randomization were determined to have new onset diabetes mellitus if (i) the subject received an anti-diabetic medication for a duration of at least 30 days or (ii) at least two fasting plasma glucose (FPG) tests indicate that FPG is >=126 mg/dL (7.0 mmol/L). New onset diabetes mellitus (NODM) = post-transplant diabetes mellitus (PTDM). The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Week 4 post-transplantation to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	162	168	156
Units: percentage of subjects
number (confidence interval 95%)
Month 12	9.9 (5.3 to 14.5)	4.2 (1.1 to 7.2)	7.1 (3 to 11.1)
Month 24	10.5 (5.8 to 15.2)	5.4 (2 to 8.8)	8.3 (4 to 12.7)
Month 36	11.1 (6.3 to 16)	6.5 (2.8 to 10.3)	10.3 (5.5 to 15)

No statistical analyses for this end point

Secondary: Percent of Subjects Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36

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End point title

Percent of Subjects Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36

End point description

The analysis was based on all subjects who had been followed up at least 1092 days after transplantation. Hypertension was defined in according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for subjects with chronic kidney disease. This definition was based upon SBP >=130 mm Hg or DBP >=80 mmHg. In addition, all subjects who had a SBP <130 mmHg and a DBP <80 mmHg who received an antihypertensive medication(s) for the indication of hypertension or with a medical history of hypertension were included in this definition. Systolic blood pressure = SBP; Diastolic blood pressure = DBP. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	182	199	192
Units: percentage of subjects
number (confidence interval 95%)	92.9 (89.12 to 96.6)	81.9 (76.56 to 87.36)	83.9 (78.65 to 89.06)

No statistical analyses for this end point

Secondary: Percent of Subjects with Incidence of Hypertension Post-Transplantation at Month 12

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End point title

Percent of Subjects with Incidence of Hypertension Post-Transplantation at Month 12

End point description

The incidence of hypertension was defined as the proportion of subjects who developed hypertension after randomization and transplantation. Specifically, the incidence of hypertension was assessed only after the Week 4 visit. This period allowed for adequate stabilization and resolution of transient changes. If subjects received antihypertensive medication for the indication of hypertension at this (or later) time point, they were considered to have developed hypertension. Hypertension was defined according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for subjects with chronic kidney disease. This definition was based upon SBP >=130 mm Hg or DBP >=80 mm Hg. Systolic blood pressure = SBP; Diastolic blood pressure = DBP. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	4	13	7
Units: percentage of subjects
number (confidence interval 95%)	75 (19.4 to 99.4)	53.8 (26.7 to 80.9)	57.1 (18.4 to 90.1)

No statistical analyses for this end point

Secondary: Percent of Subjects With Prevalence of Hypertension Post-Transplantation at Month 12

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End point title

Percent of Subjects With Prevalence of Hypertension Post-Transplantation at Month 12

End point description

The prevalence of hypertension was defined as the proportion of subjects at any given time who meet the definition of hypertension. Hypertension defined according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure for subjects with chronic kidney disease. This definition is based upon SBP >=130 mmHg or DBP >=80 mmHg. Systolic blood pressure = SBP; Diastolic blood pressure = DBP. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)	91 (87.17 to 94.73)	89.8 (85.88 to 93.76)	88.6 (84.37 to 92.8)

No statistical analyses for this end point

Secondary: Mean Systolic Blood Pressure and Diastolic Blood Pressure

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End point title

Mean Systolic Blood Pressure and Diastolic Blood Pressure

End point description

End point type

Secondary

End point timeframe

Months 12, 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	188	193	191
Units: mmHg
arithmetic mean (standard deviation)
Systolic; Month 12 (n=188, 193, 191)	138.7 ± 19.98	131.4 ± 16.54	132.7 ± 16.21
Diastolic; Month 12 (n=188, 193, 191)	81.9 ± 11.1	78.7 ± 10.91	79.3 ± 11.54
Systolic; Month 24 (n=160, 185, 174)	135.4 ± 19.71	130.5 ± 17.35	129.8 ± 16.84
Diastolic; Month 24 (n=160, 185, 174)	80.3 ± 10.2	78.3 ± 10.51	77.8 ± 10.31
Systolic; Month 36 (n=145, 180, 166)	133.5 ± 17.93	127.7 ± 16.48	126 ± 16.14
Diastolic; Month 36 (n=145, 180, 166)	79.5 ± 9.16	76.6 ± 9.75	76.1 ± 11.2

No statistical analyses for this end point

Secondary: Percent of Subjects at Baseline with Controlled Hypertension Post Transplantation by Month 12

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End point title

Percent of Subjects at Baseline with Controlled Hypertension Post Transplantation by Month 12

End point description

Controlled hypertension was defined as a SBP < 130 mm Hg and a DBP < 80 mm Hg while receiving an antihypertensive medication for the indication of hypertension or receiving an antihypertensive medication for another indication with a medical history of hypertension. Subjects with a SBP < 130 mm Hg and a DBP < 80 mm Hg who were prescribed an antihypertensive medication(s) for an indication(s) other than hypertension (eg, beta blockers for migraine prophylaxis) with no medical history of hypertension were not considered to have either hypertension or controlled hypertension. Systolic blood pressure = SBP; Diastolic blood pressure = DBP. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Day 1 to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	182	182	183
Units: percentage of subjects
number (confidence interval 95%)	21.4 (15.5 to 27.4)	28.6 (22 to 35.1)	24.6 (18.4 to 30.8)

No statistical analyses for this end point

Secondary: Percent of Subjects with Prevalence of Controlled Hypertension at Month 12

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End point title

Percent of Subjects with Prevalence of Controlled Hypertension at Month 12

End point description

The prevalence of controlled hypertension was defined as the proportion of subjects at any given time who met the definition of controlled hypertension. Controlled hypertension was defined as a SBP < 130 mm Hg and a DBP < 80 mm Hg while receiving an antihypertensive medication for the indication of hypertension or receiving an antihypertensive medication for another indication with a medical history of hypertension. Subjects with a SBP < 130 mm Hg and a DBP < 80 mm Hg who were prescribed an antihypertensive medication(s) for an indication(s) other than hypertension (eg, beta blockers for migraine prophylaxis) with no medical history of hypertension were not considered to have either hypertension or controlled hypertension. Systolic blood pressure = SBP; Diastolic blood pressure = DBP. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	186	193	190
Units: percentage of subjects
arithmetic mean (confidence interval 95%)	21 (15.12 to 26.82)	28 (21.65 to 34.31)	24.7 (18.6 to 30.87)

No statistical analyses for this end point

Secondary: Percent of Non-dyslipidemic Subjects With Incidence of Dyslipidemia Post-Transplantation by Month 12

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End point title

Percent of Non-dyslipidemic Subjects With Incidence of Dyslipidemia Post-Transplantation by Month 12

End point description

Incidence of dyslipidemia was defined as the proportion of subjects who developed dyslipidemia after randomization and transplantation. Dyslipidemia was defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia = hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). The TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Randomisation to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	75	94	79
Units: percentage of subjects
number (confidence interval 95%)	80 (70.9 to 89.1)	63.8 (54.1 to 73.5)	70.9 (60.9 to 80.9)

No statistical analyses for this end point

Secondary: Percent of Subjects With Prevalence of Dyslipidemia at Month 12

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End point title

Percent of Subjects With Prevalence of Dyslipidemia at Month 12

End point description

The prevalence of dyslipidemia was defined as the proportion of subjects at any given time who met the definition of dyslipidemia. Dyslipidemia defined in accordance with recent guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Dyslipidemia defined as hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)	52.9 (46.4 to 59.5)	44.7 (38.2 to 51.2)	46.1 (39.5 to 52.7)

No statistical analyses for this end point

Secondary: Percent of Subjects With Controlled Dyslipidemia at Month 12

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End point title

Percent of Subjects With Controlled Dyslipidemia at Month 12

End point description

Prevalence of controlled dyslipidemia = the percentage of subjects at any given time who met the stated definition of dyslipidemia. Dyslipidemia as per National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) was defined as hypertriglyceridemia (TGs >= 500 milligrams/deciliter (mg/dL) [5.65 mmol/L]), hypercholesterolemia (LDL >= 100 mg/dL [2.59 mmol/L]), or elevated non-HDL (non-HDL >= 130 mg/dL [3.36 mmol/L]) in the presence of high TGs (TGs >= 200 mg/dL [2.26 mmol/L]). Controlled dyslipidemia defined as subjects who received successful pharmacologic treatment for 1 of the above stated dyslipidemias, and their lipid values fell below the thresholds described. TG = triglyceride; LDL = low density lipoprotein; HDL = high density lipoprotein; millimole/Liter (mmol/L). For 95% CI within each group, normal approximation is used if N >=5. Otherwise exact method is used. Analysis was performed in intent-to-treat (ITT) population.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)	18.1 (13 to 23.2)	15.5 (10.8 to 20.2)	15.5 (10.7 to 20.3)

No statistical analyses for this end point

Secondary: Number of Subjects With Antihyperlipidemic Medication by Intensity Level

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End point title

Number of Subjects With Antihyperlipidemic Medication by Intensity Level

End point description

An intensity level was associated with dose level of statin based anti-hyperlipidemic agent. Any other agent (i.e., non-statin therapy) used as an antihyperlipidemic were considered Level I treatment intensity. Multiple daily doses were averaged to compute daily dose during that period. Level I = 20 mg fluvastatin (flu), 10 mg lovastatin (lova), 10 mg pravastatin (prav), 5-10 mg simvastatin (sim); Level II = 10 mg atorvastatin (atorv), 40 mg flu, 20 mg lova, 20 mg prav, 5 mg rosuvastatin (rosu), 20 mg sim, 10/10 vytorin; Level III = 20 mg atorv, 80 mg flu, 40 mg lova, 40 mg prav, 10 mg rosu, 40 mg sim, 10/20 vytorin; Level IV = 40 mg atorv, 80 mg lova, 80 mg prav, 20 mg rosu, 80 mg sim, 10/40 vytorin; Level V = 80 mg atorv, 40 mg rosu, 10/80 vytorin. Concomitant use of a statin and an agent of another class elevated the intensity level of the statin therapy by 1 level; therefore, an intensity level of greater than V was possible. Analysis was performed in ITT population.

End point type

Secondary

End point timeframe

Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	103	92	92
Units: subjects
number (not applicable)
Intensity Level I	17	15	17
Intensity Level II	46	27	39
Intensity Level III	27	32	23
Intensity Level IV	8	16	9
Intensity Level V	4	1	4
Intensity Level VI	1	1	0

No statistical analyses for this end point

Secondary: Percent of Subjects Using At Least One Anti-Hyperlipidemic Medication

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End point title

Percent of Subjects Using At Least One Anti-Hyperlipidemic Medication

End point description

This analysis is based on all subjects who were followed up at least 1092 days after transplantation. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population. Completer analysis is based on all subjects who have been followed up at least 1092 days after transplantation.

End point type

Secondary

End point timeframe

Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	182	199	192
Units: percentage of subjects
number (confidence interval 95%)	56.6 (49.4 to 63.8)	46.2 (39.3 to 53.2)	47.9 (40.9 to 55)

No statistical analyses for this end point

Secondary: Mean Value of Lipid Parameters

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End point title

Mean Value of Lipid Parameters

End point description

Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and triglycerides (TGs). The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Months 12, 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	189	195	192
Units: mg/dL
arithmetic mean (standard deviation)
non-HDL Cholesterol; Month 12 (n=189, 195, 192)	144.1 ± 47.31	131.5 ± 38.18	131.7 ± 36.76
Total Cholesterol; Month 12 (n=189, 195, 192)	191.5 ± 49.29	182.4 ± 39.78	181.3 ± 39.92
HDL Cholesterol; Month 12 (n=189, 195, 192)	47.4 ± 13.33	50.8 ± 15.98	49.7 ± 15.69
LDL Cholesterol; Month 12 (n=187, 186, 183)	107.3 ± 39.6	102.1 ± 33.4	100.8 ± 29.48
Triglyceride; Month 12 (n=187, 186, 183)	184.6 ± 106.42	149.4 ± 87.25	155 ± 85.08
non-HDL Cholesterol; Month 24 (n=166, 190, 181)	145.1 ± 39.52	126.7 ± 38.48	127 ± 36.76
Total Cholesterol; Month 24 (n=166, 190, 181)	193.5 ± 40.23	175.3 ± 42.38	175.4 ± 40.03
HDL ; Month 24 (n=166, 190, 181)	48.4 ± 13.74	48.6 ± 15.28	48.5 ± 14.92
LDL Cholesterol; Month 24 (n=164, 186, 168)	109.1 ± 35.92	98.6 ± 33.71	96.5 ± 30.52
Triglyceride; Month 24 (n=164, 186, 168)	179.5 ± 97.51	143.4 ± 88.97	151.2 ± 95.88
non-HDL Cholesterol; Month 36 (n=154, 184, 176)	142.2 ± 43.19	122.4 ± 40.12	122.1 ± 38.78
Total Cholesterol; Month 36 (n=154, 184, 176)	190.7 ± 45.28	171.3 ± 45.78	170.7 ± 43.26
HDL Cholesterol; Month 36 (n=154, 184, 176)	48.5 ± 14.27	48.9 ± 15.37	48.6 ± 16.86
LDL Cholesterol; Month 36 (n=142, 170, 161)	107.6 ± 37.66	96.7 ± 36.53	92.5 ± 33.78
Triglyceride; Month 36 (n=142, 170, 161)	179.1 ± 97.07	132.7 ± 68.69	144 ± 81.48

No statistical analyses for this end point

Secondary: Percent of Subjects with Prevalence of Acute Rejection (AR) by Month 36

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End point title

Percent of Subjects with Prevalence of Acute Rejection (AR) by Month 36

End point description

Prevalence of AR = subjects with the stated definition of AR at any given time. AR=clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each subject was counted. Clinical evidence=if either a or b was satisfied: a: an unexplained rise of serum creatinine >=25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. ITT Population was analysed.

End point type

Secondary

End point timeframe

Randomization to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)
Month 6 (n=221, 226, 219)	5.4 (2.4 to 8.4)	16.8 (11.9 to 21.7)	21.9 (16.4 to 27.4)
Month 24 (n=221, 226, 219)	9 (5.3 to 12.8)	17.3 (12.3 to 22.2)	24.2 (18.5 to 29.9)
Month 36 (n=221, 226, 219)	9.5 (5.6 to 13.4)	17.3 (12.3 to 22.2)	24.2 (18.5 to 29.9)

No statistical analyses for this end point

Secondary: Number of Subjects with Acute Rejection (AR) Post-transplant in Terms of Severity using Banff Grades by Month 36

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End point title

Number of Subjects with Acute Rejection (AR) Post-transplant in Terms of Severity using Banff Grades by Month 36

End point description

Acute rejection was defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Clinical evidence defined: if either a or b was satisfied: a) an unexplained rise of serum creatinine >=25% from baseline creatinine; b) an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Only the episode with the highest Banff grade for each subject was counted. Analysis was performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Randomisation to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: subjects
number (not applicable)
Mild Acute (IA); Month 6	1	4	7
Mild Acute (IB); Month 6	5	9	3
Moderate Acute (IIA); Month 6	5	14	16
Moderate Acute (IIB); Month 6	1	10	20
Severe Acute (III); Month 6	0	1	2
Mild Acute (IA); Month 12	3	4	7
Mild Acute (IB); Month 12	5	8	3
Moderate Acute (IIA); Month 12	6	16	17
Moderate Acute (IIB); Month 12	2	10	20
Severe Acute (III); Month 12	0	1	2
Mild Acute (IA); Month 24	4	4	7
Mild Acute (IB); Month 24	7	8	3
Moderate Acute (IIA); Month 24	6	16	18
Moderate Acute (IIB); Month 24	3	10	22
Severe Acute (III); Month 24	0	1	3
Mild Acute (IA); Month 36	5	4	7
Mild Acute (IB); Month 36	7	8	3
Moderate Acute (IIA); Month 36	6	16	18
Moderate Acute (IIB); Month 36	3	10	22
Severe Acute (III); Month 36	0	1	3

No statistical analyses for this end point

Secondary: Percent of Subjects Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12

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End point title

Percent of Subjects Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12

End point description

Subject were considered to have delayed graft function (DGF), if treated with dialysis within the first week (Day 1 - 8) after transplantation. Use of polyclonal antilymphocyte preparations (LDT) was permitted only for subjects randomised to cyclosporine (CsA) who experienced impaired renal allograft function and anticipated DGF following transplantation and were not permitted in belatacept-treated subjects, except for the treatment of acute rejection. Subjects treated with LDT began CsA at the discretion of the investigator by Day 7. LDT could also have been used in subjects who met >=1 of the following criteria, observed in the presence of a transplant artery and vein and no evidence of hydronephrosis by sonogram: Urine output < 250 mL/12 hours, no significant improvement (<1 milligram per deciliter (mg/dL)) in serum creatinine from baseline value over the first 24 - 72 hours post-transplant, or dialysis treatment. Analysis was performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Randomisation to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)	3.6 (1.2 to 6.1)	0.4 (0 to 2.4)	0.5 (0 to 2.5)

No statistical analyses for this end point

Secondary: Percent of Subjects Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36

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End point title

Percent of Subjects Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36

End point description

LDT (thymoglobulin or antithymocyte gamma globulin [ATGAM]) was permitted only for subjects randomized to cyclosporine (CsA) who experienced impaired renal allograft function and anticipated delayed graft function post transplantation. Acute rejection (AR) defined as clinico-pathological event requiring clinical evidence (an unexplained rise of serum creatinine >=25% from baseline or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed) and biopsy confirmation. AR defined by renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, higher scores indicating more severe rejection. Banff 97 category is an international standardized histopathological classification. Only the episode with the highest Banff grade for each subject was counted. Analysis was per performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Randomisation to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (not applicable)
Month 6	0.5	4.4	5.9
Month 12	0.9	4.4	5.9
Month 24	1.4	4.4	5.9
Month 36	1.8	4.4	5.9

No statistical analyses for this end point

Secondary: Percent of Subjects with Corticosteroid resistant Acute Rejection (AR) by Month 36

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End point title

Percent of Subjects with Corticosteroid resistant Acute Rejection (AR) by Month 36

End point description

Steroid-resistant acute rejection (AR) defined as use of lymphocyte-depletion therapy following treatment with corticosteroids. AR defined as clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Clinical evidence defined as an unexplained rise of serum creatinine >=25% from baseline creatinine; or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 international standardized histopathological working classification of kidney transplant pathology. Only the episode with the highest Banff grade for each subject was counted. Analysis was per performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Randomisation to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (not applicable)
Month 6	0	4	5.9
Month 12	0	5.3	6.4
Month 24	0.5	5.3	6.4
Month 36	0.5	5.3	6.8

No statistical analyses for this end point

Secondary: Number of Subjects Who Recovered Completely from an Episode of Acute Rejection (AR) by Month 12

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End point title

Number of Subjects Who Recovered Completely from an Episode of Acute Rejection (AR) by Month 12

End point description

Acute rejection (AR)= clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater. Clinical evidence = unexplained rise of serum creatinine >=25% from baseline; or unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Complete recovery following AR defined as serum creatinine [SCr] levels returned to baseline. Recovery calculated using 2 algorithms: Algorithm 1 = last laboratory measurement prior to onset of AR (baseline and first laboratory measurement after 84 days since onset of AR = resolution); Algorithm 2 = lowest lab measurement on or after transplantation and prior to onset day of AR (baseline and lowest laboratory measurement after onset on first AR up to Month 12 = resolution). Analysis was per performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Randomisation to Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	16	39	48
Units: subjects
number (not applicable)
Algorithm 1	13	29	39
Algorithm 2	13	34	43

No statistical analyses for this end point

Secondary: Percent of Subjects with Subclinical Rejection at Month 12

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End point title

Percent of Subjects with Subclinical Rejection at Month 12

End point description

Subclinical rejection defined as histological findings by the central pathologist consistent with acute rejection, but lacking its clinical correlate. Acute rejection defined as a clinico-pathological event requiring clinical evidence and renal biopsy confirmation demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each subject was counted. Clinical evidence defined as an unexplained rise of serum creatinine >=25% from baseline; or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of acute rejection existed. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Analysis was per performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Month 12

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	155	170	164
Units: percentage of subjects
number (confidence interval 95%)	5.2 (1.7 to 8.6)	4.7 (1.5 to 7.9)	4.3 (1.2 to 7.4)

No statistical analyses for this end point

Secondary: Number of Subjects Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36

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End point title

Number of Subjects Treated for Acute Rejection (AR) Regardless of Histological Findings by Month 36

End point description

Allograft rejection includes any episode of rejection: clinically suspected rejection, treated rejection, any central biopsy-proven acute rejection (BPAR), and acute rejection (AR: a subset of BPAR) defined as central biopsy-proven rejection that was either clinically suspected by protocol-defined reasons or by other reasons and was treated. AR defined as clinico-pathological event requiring clinical evidence ( either an unexplained rise of serum creatinine >=25% from baseline or an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remained elevated within 14 days post-transplantation and clinical suspicion of AR) and renal biopsy confirmation biopsy demonstrating a Banff 97 classification of kidney transplant pathology classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the highest Banff grade for each subject was counted. Analysis was per performed in all randomised and transplanted subjects.

End point type

Secondary

End point timeframe

Randomisation to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: subjects
number (not applicable)
Month 6	43	68	70
Month 12	56	72	75
Month 24	63	74	81
Month 36	69	76	82

No statistical analyses for this end point

Secondary: Mean Value of Physical and Mental Components using SF-36 Questionnaire

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End point title

Mean Value of Physical and Mental Components using SF-36 Questionnaire

End point description

The SF-36 was a Subject-Reported Quality of Life (QoL) Short Form (SF) questionnaire. The scale in the mental component (MCS) part of the instrument ranged from 1 to 6 with 1=all of the time and 6= none of the time. The scale for physical component (PCS) ranged from 1 to 3 with 1=Yes, limited a lot and 3=No, not limited at all. The scale for the extent that physical health or emotional problems interfered with normal activities ranged from 1 to 5 with 1=not at all and 5= extremely. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Months 6, 12, 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	203	218	201
Units: units on a scale
arithmetic mean (standard deviation)
Mental Component Score; Month 6 (n=191, 205, 189)	49.4 ± 11.08	49.9 ± 10.55	51.1 ± 10.53
Physical Component Score; Month 6 (n=191,205,189)	47.3 ± 8.91	48.9 ± 8.59	49.2 ± 7.58
Mental Component Score; Month 12 (n=198,210,194)	49.5 ± 10.78	50.3 ± 10.08	49.9 ± 10.54
Physical Component Score; Month 12 (n=198,210,194)	47.5 ± 9.34	49.6 ± 8.18	50.3 ± 8.21
Mental Component Score; Month 24 (n=200,214,198)	48.3 ± 11.14	49.6 ± 10.77	48.8 ± 11.03
Physical Component Score; Month 24 (n=200,214,198)	47.3 ± 9.5	49 ± 8.77	49.9 ± 8.03
Mental Component Score; Month 36 (n=203,218,201)	46.9 ± 11.6	48.7 ± 11.26	48.3 ± 11.5
Physical Component Score; Month 36 (n=203,218,201)	47.1 ± 9.47	49.2 ± 9.15	48.7 ± 8.9

No statistical analyses for this end point

Secondary: Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire

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End point title

Mean Value of the Eight Domain Scores of Quality of Life Using SF-36 Questionnaire

End point description

Subject-Reported questionnaire (8 Domains): Bodily Pain (1=none to 6=very severe;Pain interfered with normal work 1=not at all to 6=extremely),General Health (1=excellent/better than 1 year ago to 5=poor /much worse than 1 year ago), Mental Health (involving emotions 1=all of the time and 6= none of the time;emotional problems interfered with normal activities 1=not at all and 5= extremely.), Physical Functioning (1 to 3 with 1=Yes,limited a lot and 3=No,not limited at all;physical health interfered with normal activities 1=not at all and 5= extremely. Role Emotional (emotional problems interfered 1=all time to 5=none of time),Role Physical (physical problems interfered 1=all time to 5=none of time),Social Functioning (interference in social activities 1=not at all to 5=extremely),Vitality: I get sick easier;I'm healthy as anyone;health excellent;expect health to worsen:1=definitely true,2=mostly true, don't know=3,mostly false=4,definitely false=5. Analysis = ITT population.

End point type

Secondary

End point timeframe

Months 6, 12, 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	205	219	206
Units: units on a scale
arithmetic mean (standard deviation)
Bodily Pain, Month 6 (n=193, 207, 193)	50.6 ± 10.96	52.5 ± 10.1	52.7 ± 10.04
General Health, Month 6 (n=193, 207, 194)	47.9 ± 10.08	48.2 ± 9.67	49 ± 8.66
Mental Health, Month 6 (n=192, 206, 194)	50.1 ± 11.08	50.3 ± 10.33	51.3 ± 10.78
Physical Functioning, Month 6 (n=193, 207, 194)	47.4 ± 9.13	48.3 ± 9.01	48 ± 8.81
Role Emotional, Month 6 (n=192, 206, 191)	44.6 ± 12.31	46 ± 11.19	46.8 ± 10.55
Role-Physical, Month 6 (n=192, 207, 192)	43.2 ± 11.08	45.2 ± 10.34	46.7 ± 9.06
Social Functioning, Month 6 (n=193, 207, 194)	47.5 ± 10.68	47.8 ± 10.41	47.9 ± 10.65
Vitality, Month 6 (n=192, 206, 194)	54 ± 10.27	55.5 ± 9.75	56.2 ± 9.29
Bodily Pain, Month 12 (n=200, 213, 199)	50.8 ± 10.79	52.7 ± 9.67	53.7 ± 9.6
General Health, Month 12 (n=200, 214, 199)	46.9 ± 9.98	48.8 ± 9.57	49.2 ± 8.85
Mental Health, Month 12 (n=200, 213, 199)	49.8 ± 10.99	50.7 ± 10.64	50.3 ± 10.29
Physical Functioning, Month 12 (n=200, 214, 198)	47.2 ± 9.77	49 ± 8.88	48.1 ± 9.84
Role Emotional, Month 12 (n=198, 213, 196)	45.8 ± 11.36	46.8 ± 10.82	45.9 ± 11.27
Role-Physical, Month 12 (n=199, 213, 196)	45 ± 10.78	47.1 ± 10	47.5 ± 9.9
Social Functioning, Month 12 (n=200, 213, 199)	47.6 ± 10.26	48.4 ± 9.61	49.1 ± 9.8
Vitality, Month 12 (n=200, 213, 199)	53.3 ± 10.01	55.7 ± 9.81	56 ± 9.34
Bodily Pain, Month 24 (n=203, 219, 205)	51 ± 10.82	51.4 ± 10.51	52.5 ± 10.47
General Health, Month 24 (n=203, 219, 205)	46.2 ± 10.07	48.4 ± 9.61	48.7 ± 9.45
Mental Health, Month 24 (n=201, 215, 199)	48.5 ± 11.13	49.7 ± 10.89	49.3 ± 10.85
Physical Functioning, Month 24 (n=203, 219, 205)	46.5 ± 10.69	48.7 ± 9.76	48 ± 10.24
Role Emotional, Month 24 (n=202, 218, 205)	44.8 ± 12.54	46.4 ± 10.89	46 ± 10.88
Role-Physical, Month 24 (n=203, 219, 204)	44.1 ± 11.61	46.6 ± 10.39	48 ± 9.33
Social Functioning, Month 24 (n=203, 219, 205)	47.3 ± 10.64	48.6 ± 10.28	47.7 ± 10.23
Vitality, Month 24 (n=201, 215, 200)	52.5 ± 10.58	54.5 ± 10.3	54.2 ± 10.3
Bodily Pain, Month 36 (n=204, 219, 205)	50 ± 11.4	52.3 ± 10.4	51 ± 11.05
General Health, Month 36 (n=205, 219, 206)	45.5 ± 10.12	47.7 ± 10.45	47.5 ± 9.93
Mental Health, Month 36 (n=203, 219, 204)	47.4 ± 11.64	48.9 ± 11.52	48.7 ± 11.43
Physical Functioning, Month 36 (n=204, 218, 206)	46.8 ± 9.92	48.1 ± 10.22	47.8 ± 10.12
Role Emotional, Month 36 (n=204, 219, 205)	43.5 ± 12.18	46 ± 11.85	45.3 ± 11.67
Role-Physical, Month 36 (n=204, 219, 205)	43.6 ± 10.73	46.3 ± 11.03	46.2 ± 10.03
Social Functioning, Month 36 (n=204, 219, 206)	46.6 ± 10.68	48.1 ± 10.28	47.1 ± 10.66
Vitality, Month 36 (n=203, 219, 204)	51.4 ± 10.48	53.6 ± 11.38	53.4 ± 10.46

No statistical analyses for this end point

Secondary: Mean Relative to an Identified Distribution (ridit) Value of Symptom Occurrence and Symptom Distress using Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSDS-59R)

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End point title

Mean Relative to an Identified Distribution (ridit) Value of Symptom Occurrence and Symptom Distress using Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSDS-59R)

End point description

Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) was used to assess occurrence (never, occasionally, regularly, almost always, always) and distress (0=no distress to 4=terrible distress) of symptoms associated with immunosuppressive therapies. Ridit (relative to an identified distribution) analysis (Fleiss JL. Statistical methods for rates and proportions. New York: John Wiley & Sons, Inc. 1991) was used. Ridit scores were calculated at baseline and at 6, 12, 24, and 36 months for overall symptom occurrence score and overall symptom distress. Ridit score reflects the probability that a score observed for an individual randomly selected from a group would be higher (worse symptom) than a score observed for a randomly selected individual from the reference group. Reference group was constituted by the frequency distribution of responses of all subjects on all items at baseline. Ridit of the reference group is by definition, 0.5. Analysis = ITT population.

End point type

Secondary

End point timeframe

Months 6, 12, 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	186	197	187
Units: Ridit score
arithmetic mean (standard error)
Symptom Distress, Month 6 (n=157, 164, 155)	0.4643 ± 0.00452	0.4407 ± 0.00404	0.4451 ± 0.00422
Symptom Occurrence, Month 6 (n=166, 176, 165)	0.4721 ± 0.00463	0.4495 ± 0.00425	0.4459 ± 0.00432
Symptom Distress, Month 12 (n=169, 185, 169)	0.4751 ± 0.00453	0.451 ± 0.00397	0.4546 ± 0.00421
Symptom Occurrence, Month 12 (n=173, 188, 173)	0.4776 ± 0.00458	0.4519 ± 0.00411	0.4525 ± 0.0043
Symptom Distress, Month 24 (n=182, 195, 179)	0.4798 ± 0.00443	0.4584 ± 0.00397	0.4646 ± 0.00424
Symptom Occurrence, Month 24 (n=184, 197, 184)	0.4804 ± 0.00446	0.4574 ± 0.00406	0.4593 ± 0.00423
Symptom Distress, Month 36 (n=184, 196, 183)	0.5 ± 0.00456	0.4746 ± 0.00408	0.4892 ± 0.00442
Symptom Occurrence, Month 36 (n=186, 197, 187)	0.5 ± 0.00459	0.4732 ± 0.00421	0.4846 ± 0.00441

No statistical analyses for this end point

Secondary: Mean Changes in the Value of Physical and Mental Components Using SF-36 from Baseline Up To Months 6, 12, 24, and 36

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End point title

Mean Changes in the Value of Physical and Mental Components Using SF-36 from Baseline Up To Months 6, 12, 24, and 36

End point description

End point type

Secondary

End point timeframe

Baseline to Months 6, 12, 24,and 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	192	203	193
Units: units on a scale
arithmetic mean (standard deviation)
Mental Component Score; Month 6 (n=187, 197, 184)	5.4 ± 0.714	6.2 ± 0.695	7.3 ± 0.72
Physical Component Score; Month 6 (n=187, 197, 184	5 ± 0.58	6.2 ± 0.566	6.7 ± 0.585
Mental Component Score; Month 12 (n=192, 200, 189)	5.4 ± 0.687	6.8 ± 0.673	6.2 ± 0.693
Physical Component Score; Month 12 (n=192,200,189)	5.5 ± 0.589	7.1 ± 0.577	7.8 ± 0.594
Mental Component Score; Month 24 (n=191,202,193)	4.4 ± 0.732	5.7 ± 0.712	5.1 ± 0.728
Physical Component Score; Month 24 (n=191,202,193)	5.1 ± 0.601	6.5 ± 0.584	7.3 ± 0.597
Mental Component Score; Month 36 (n=190,203,191)	2.6 ± 0.756	5.1 ± 0.732	4.5 ± 0.754
Physical Component Score; Month 36 (n=190,203,191)	4.9 ± 0.633	6.5 ± 0.612	6.1 ± 0.631

No statistical analyses for this end point

Secondary: Mean Change in the Value of the Eight Domain Scores Using SF-36 from Baseline Up To Months 6, 12, 24, and 36

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End point title

Mean Change in the Value of the Eight Domain Scores Using SF-36 from Baseline Up To Months 6, 12, 24, and 36

End point description

End point type

Secondary

End point timeframe

Baseline to Months 6, 12, 24, and 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	194	207	197
Units: units on a scale
arithmetic mean (standard error)
Bodily Pain, Month 6 (n=189,201,189)	2.9 ± 0.712	4.5 ± 0.691	4.6 ± 0.712
General Health, Month 6 (n=189,201,190)	6.7 ± 0.631	7.1 ± 0.612	7.3 ± 0.63
Mental Health, Month 6 (n=188,198,190)	4.7 ± 0.716	5.2 ± 0.698	6.1 ± 0.712
Physical Functioning, Month 6 (n=189,201,190)	4.7 ± 0.61	5.3 ± 0.592	5.6 ± 0.61
Role Emotional, Month 6 (n=188,200,186)	4.7 ± 0.767	5.8 ± 0.744	6.9 ± 0.772
Role-Physical, Month 6 (n=188,201,187)	6.4 ± 0.718	8.4 ± 0.694	9.6 ± 0.72
Social Functioning, Month 6 (n=189,201,190)	6 ± 0.724	6.8 ± 0.702	6.9 ± 0.722
Vitality, Month 6 (n=188,198,190)	7.5 ± 0.668	9 ± 0.651	9.9 ± 0.665
Bodily Pain, Month 12 (n=194,205,195)	3.1 ± 0.665	4.8 ± 0.647	5.5 ± 0.664
General Health, Month 12 (n=194,206,195)	6 ± 0.638	7.7 ± 0.619	7.6 ± 0.636
Mental Health, Month 12 (n=194,203,195)	4.4 ± 0.685	6 ± 0.67	5 ± 0.684
Physical Functioning, Month 12 (n=194,206,194)	4.7 ± 0.64	6.2 ± 0.621	5.8 ± 0.641
Role Emotional, Month 12 (n=192,205,191)	5.7 ± 0.765	6.6 ± 0.741	5.9 ± 0.768
Role-Physical, Month 12 (n=193,205,191)	8.3 ± 0.716	10.3 ± 0.695	10.4 ± 0.72
Social Functioning, Month 12 (n=194,205,195)	6.4 ± 0.669	7.7 ± 0.65	8 ± 0.667
Vitality, Month 12 (n=194,203,195)	7 ± 0.651	9.2 ± 0.636	9.7 ± 0.649
Bodily Pain, Month 24 (n=192,207,197)	3.2 ± 0.722	3.3 ± 0.696	4.1 ± 0.713
General Health, Month 24 (n=193,207,197)	5.1 ± 0.641	7.2 ± 0.619	6.8 ± 0.635
Mental Health, Month 24 (n=193,203,195)	3.2 ± 0.71	4.6 ± 0.692	4 ± 0.706
Physical Functioning, Month 24 (n=193,207,197)	4.1 ± 0.685	5.7 ± 0.662	5.5 ± 0.679
Role Emotional, Month 24 (n=192,206,196)	4.7 ± 0.793	6 ± 0.766	5.9 ± 0.785
Role-Physical, Month 24 (n=193,207,195)	7.4 ± 0.74	9.4 ± 0.715	10.7 ± 0.737
Social Functioning, Month 24 (n=193, 207,197)	5.9 ± 0.722	7.4 ± 0.697	6.3 ± 0.715
Vitality, Month 24 (n=193,203,196)	6.2 ± 0.7	7.9 ± 0.682	8 ± 0.695
Bodily Pain, Month 36 (n=191,207,196)	2.3 ± 0.739	4.2 ± 0.71	3 ± 0.73
General Health, Month 36 (n=193,207,197)	4.1 ± 0.681	6.6 ± 0.657	5.8 ± 0.674
Mental Health, Month 36 (n=191,204,195)	1.8 ± 0.754	4.1 ± 0.729	3.4 ± 0.746
Physical Functioning, Month 36 (n=192,206,197)	4.4 ± 0.692	5.3 ± 0.668	5.1 ± 0.684
Role Emotional, Month 36 (n=192,207,195)	3.3 ± 0.83	5.6 ± 0.8	5 ± 0.824
Role-Physical, Month 36 (n=192,207,195)	6.8 ± 0.754	9.2 ± 0.727	8.9 ± 0.749
Social Functioning, Month 36 (n=192,207,197)	5.1 ± 0.736	7 ± 0.708	5.6 ± 0.726
Vitality, Month 36 (n=191,204,195)	4.9 ± 0.721	7.3 ± 0.698	7.3 ± 0.714

No statistical analyses for this end point

Secondary: Percent of Subjects Surviving With a Functioning Graft

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End point title

Percent of Subjects Surviving With a Functioning Graft

End point description

End point type

Secondary

End point timeframe

Months 24, 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)
Month 24	90.5 (86.6 to 94.4)	94.7 (91.8 to 97.6)	94.1 (90.9 to 97.2)
Month 36	88.7 (84.5 to 92.9)	92 (88.5 to 95.6)	92.2 (88.7 to 95.8)

No statistical analyses for this end point

Secondary: Percent of Subjects with Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36

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End point title

Percent of Subjects with Composite Endpoint or Death, Graft Loss or Acute Rejection by Month 36

End point description

Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine (SCr) >=6.0 milligrams per deciliter (mg/dL) or 530 micromoles per liter (μmol/L) as determined by the central laboratory for >=4 weeks or >=56 consecutive days of dialysis or impairment of renal function to such a degree that the subject underwent retransplant. Acute rejection was defined as central biopsy proven rejection that was either (1) clinically suspected by protocol defined reasons or (2) clinically suspected by other reasons and treated. Death and graft loss were not imputed. The analysis was performed in all randomised and transplanted subjects, intent to treat (ITT) population.

End point type

Secondary

End point timeframe

Randomisation to Month 36

End point values	Cyclosporine	Belatacept LI	Belatacept MI
Number of subjects analysed	221	226	219
Units: percentage of subjects
number (confidence interval 95%)
Month 12	13.6 (9.1 to 18.1)	19.5 (14.3 to 24.6)	25.1 (19.4 to 30.9)
Month 24	18.1 (13 to 23.2)	19.9 (14.7 to 25.1)	27.9 (21.9 to 33.8)
Month 36	19.9 (14.6 to 25.2)	20.8 (15.5 to 26.1)	28.3 (22.3 to 34.3)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Randomisation to study completion (approximately 10 years)

Adverse event reporting additional description

Study start: March 2005; Study Completion: April 2015. All randomised and transplanted subjects, intent to treat (ITT) population

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Cyclosporine

Reporting group description

Reporting group title

Belatacept - MI

Reporting group description

Reporting group title

Belatacept - LI

Reporting group description

Serious adverse events	Cyclosporine	Belatacept - MI	Belatacept - LI
Total subjects affected by serious adverse events
subjects affected / exposed	167 / 215 (77.67%)	164 / 219 (74.89%)	160 / 226 (70.80%)
number of deaths (all causes)	26	19	15
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lip squamous cell carcinoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastatic uterine cancer
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Metastases to lung
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	2 / 3	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal oncocytoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thyroid cancer
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anogenital warts
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Brain neoplasm
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Iris neoplasm
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Pancreatic neoplasm
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Sarcoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Throat cancer
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Adenoma benign
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Basosquamous carcinoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	12 / 215 (5.58%)	8 / 219 (3.65%)	9 / 226 (3.98%)
occurrences causally related to treatment / all	19 / 27	15 / 21	9 / 16
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastatic malignant melanoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic adenoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lung cancer metastatic
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Post transplant lymphoproliferative disorder
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	2 / 2	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin cancer
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acanthoma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Benign breast neoplasm
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder adenocarcinoma stage unspecified
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Chronic myeloid leukaemia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	9 / 215 (4.19%)	9 / 219 (4.11%)	8 / 226 (3.54%)
occurrences causally related to treatment / all	19 / 22	15 / 21	6 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thymic cancer metastatic
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastatic squamous cell carcinoma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-small cell lung cancer
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Oesophageal carcinoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Squamous cell carcinoma
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
B-cell lymphoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cervix carcinoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemangioma of liver
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malignant pleural effusion
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Keratoacanthoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parathyroid tumour benign
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder papilloma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bowen's disease
subjects affected / exposed	2 / 215 (0.93%)	3 / 219 (1.37%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	4 / 4	5 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal neoplasm
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Femoral artery occlusion
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	4 / 215 (1.86%)	3 / 219 (1.37%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	3 / 4	0 / 3	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infarction
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arterial stenosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphocele
subjects affected / exposed	8 / 215 (3.72%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 8	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arterial thrombosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Embolism venous
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic venous thrombosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery dissection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular compression
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive emergency
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Phlebitis superficial
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Shock haemorrhagic
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Capillary leak syndrome
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombophlebitis superficial
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arterial occlusive disease
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	4 / 215 (1.86%)	5 / 219 (2.28%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 4	1 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombophlebitis
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic stenosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Hyperthermia
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumatosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ulcer
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Accidental death
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Hernia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 2	2 / 2
deaths causally related to treatment / all	0 / 1	0 / 2	2 / 2
Incarcerated hernia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malaise
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	16 / 215 (7.44%)	13 / 219 (5.94%)	17 / 226 (7.52%)
occurrences causally related to treatment / all	6 / 22	4 / 14	5 / 19
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chest discomfort
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	6 / 215 (2.79%)	6 / 219 (2.74%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 9	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inflammation
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multi-organ failure
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral swelling
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza like illness
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic ulcer
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Transplant rejection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Drug hypersensitivity
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal transplant failure
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic allograft nephropathy
subjects affected / exposed	4 / 215 (1.86%)	4 / 219 (1.83%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	1 / 4	0 / 4	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Acquired hydrocele
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 3	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vaginal haemorrhage
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Breast calcifications
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Priapism
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metrorrhagia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Benign prostatic hyperplasia
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endometriosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Laryngeal oedema
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory arrest
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis chronic
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 4	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Pulmonary hypertension
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Pulmonary oedema
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute pulmonary oedema
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary congestion
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Bullous lung disease
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mania
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute psychosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Completed suicide
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hallucination
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mental disorder
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypomania
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Alcoholism
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Panic attack
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood glucose fluctuation
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	2 / 215 (0.93%)	6 / 219 (2.74%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 4	0 / 7	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood creatine increased
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	10 / 18	0 / 5	4 / 14
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Blood culture positive
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus test positive
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Polyomavirus test positive
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 10	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumocystis test positive
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 10	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Ultrasound kidney abnormal
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 0	1 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood glucose decreased
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coagulation test abnormal
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	16 / 215 (7.44%)	5 / 219 (2.28%)	10 / 226 (4.42%)
occurrences causally related to treatment / all	10 / 18	0 / 5	4 / 14
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcus test positive
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 3	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Delayed graft function
subjects affected / exposed	9 / 215 (4.19%)	2 / 219 (0.91%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	1 / 9	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postoperative wound complication
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal lymphocele
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Soft tissue injury
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transplant dysfunction
subjects affected / exposed	7 / 215 (3.26%)	3 / 219 (1.37%)	5 / 226 (2.21%)
occurrences causally related to treatment / all	4 / 7	1 / 3	2 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transplant failure
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureteric anastomosis complication
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Face injury
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Graft complication
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 215 (0.00%)	4 / 219 (1.83%)	7 / 226 (3.10%)
occurrences causally related to treatment / all	0 / 0	1 / 4	4 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haematuria
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	1 / 215 (0.47%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriovenous fistula aneurysm
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chest injury
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Patella fracture
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Complications of transplanted kidney
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Transfusion reaction
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 0	0 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound evisceration
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Complications of transplant surgery
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Excoriation
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Laceration
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural inflammation
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seroma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary anastomotic leak
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular graft complication
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriovenous fistula occlusion
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stenosis of vesicourethral anastomosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Carbon monoxide poisoning
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Graft loss
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postoperative ileus
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Procedural hypotension
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	9 / 215 (4.19%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	9 / 9	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Congenital cystic kidney disease
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Polycystic liver disease
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Patent ductus arteriosus
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	2 / 215 (0.93%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	1 / 8	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiogenic shock
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mitral valve disease
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Cardiac failure
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Left ventricular dysfunction
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic valve disease
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	8 / 215 (3.72%)	3 / 219 (1.37%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 9	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 6	0 / 3	0 / 2
Myocardial ischaemia
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	5 / 215 (2.33%)	4 / 219 (1.83%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	2 / 6	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1	0 / 0
Coronary artery disease
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulseless electrical activity
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 215 (0.47%)	6 / 219 (2.74%)	5 / 226 (2.21%)
occurrences causally related to treatment / all	0 / 1	0 / 7	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	3 / 215 (1.40%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Headache
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Amnesia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intracranial pressure increased
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Central nervous system lesion
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Carotid artery stenosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	2 / 215 (0.93%)	5 / 219 (2.28%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 2	1 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pineal gland cyst
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	3 / 215 (1.40%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Action tremor
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myasthenic syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral haematoma
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cervicobrachial syndrome
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mononeuropathy
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Agranulocytosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	4 / 215 (1.86%)	4 / 219 (1.83%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 4	2 / 4	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemolytic uraemic syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	7 / 215 (3.26%)	7 / 219 (3.20%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	1 / 9	2 / 7	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bicytopenia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 215 (0.47%)	4 / 219 (1.83%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 1	0 / 5	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Splenic cyst
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aplasia pure red cell
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 215 (0.00%)	4 / 219 (1.83%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	2 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Deafness
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Motion sickness
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Middle ear effusion
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal vein occlusion
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Papilloedema
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vision blurred
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vitreous haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Ascites
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic gastroparesis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis erosive
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hernial eventration
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tongue ulceration
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	3 / 215 (1.40%)	3 / 219 (1.37%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 3	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	5 / 219 (2.28%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	3 / 215 (1.40%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatolithiasis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Volvulus
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	8 / 215 (3.72%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 9	1 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	9 / 215 (4.19%)	9 / 219 (4.11%)	12 / 226 (5.31%)
occurrences causally related to treatment / all	1 / 10	2 / 12	1 / 12
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Incarcerated inguinal hernia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Intestinal haemorrhage
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Gastrointestinal disorder
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	4 / 48	10 / 58	2 / 33
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Retroperitoneal haematoma
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastric ulcer perforation
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Irritable bowel syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 215 (0.47%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	1 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombosis mesenteric vessel
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Abdominal compartment syndrome
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intra-abdominal haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mesenteric arterial occlusion
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Small intestinal obstruction
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Toothache
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	5 / 215 (2.33%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	2 / 5	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis alcoholic
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bile duct obstruction
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic function abnormal
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatosplenomegaly
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gallbladder disorder
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bile duct stenosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bile duct stone
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin ulcer
subjects affected / exposed	0 / 215 (0.00%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ingrowing nail
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pruritus
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rash generalised
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subcutaneous emphysema
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Actinic keratosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Erythema multiforme
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	13 / 215 (6.05%)	6 / 219 (2.74%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	5 / 20	0 / 6	2 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal artery thrombosis
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureteric obstruction
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glomerulonephritis acute
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	2 / 215 (0.93%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	6 / 215 (2.79%)	5 / 219 (2.28%)	7 / 226 (3.10%)
occurrences causally related to treatment / all	6 / 6	1 / 5	1 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal tubular disorder
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 2	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Azotaemia
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Obstructive uropathy
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cyst
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal haematoma
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureteric stenosis
subjects affected / exposed	5 / 215 (2.33%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vesicoureteric reflux
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephritis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal mass
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal artery stenosis
subjects affected / exposed	2 / 215 (0.93%)	3 / 219 (1.37%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal tubular necrosis
subjects affected / exposed	4 / 215 (1.86%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	3 / 4	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary incontinence
subjects affected / exposed	1 / 215 (0.47%)	3 / 219 (1.37%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute prerenal failure
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glomerulonephritis membranous
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	4 / 215 (1.86%)	4 / 219 (1.83%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal vein thrombosis
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal cyst ruptured
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary bladder polyp
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureteric haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Focal segmental glomerulosclerosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Proteinuria
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	2 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal haemorrhage
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal tubular atrophy
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary fistula
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinoma
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anuria
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder neck sclerosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephropathy
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary bladder haemorrhage
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ureteral necrosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hyperparathyroidism
subjects affected / exposed	5 / 215 (2.33%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperparathyroidism tertiary
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Groin pain
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bursitis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diastasis recti abdominis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neuropathic arthropathy
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Acinetobacter infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Abdominal sepsis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriovenous graft site infection
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Encephalitis meningococcal
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Furuncle
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis E
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Histoplasmosis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	2 / 215 (0.93%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 2	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Periodontitis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	0 / 3	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 215 (0.00%)	3 / 219 (1.37%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Tuberculosis of intrathoracic lymph nodes
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tuberculosis gastrointestinal
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection enterococcal
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Varicella zoster virus infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vulval abscess
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bone tuberculosis
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	4 / 215 (1.86%)	3 / 219 (1.37%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	3 / 7	2 / 5	3 / 4
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 4	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fungal skin infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	7 / 215 (3.26%)	9 / 219 (4.11%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 7	2 / 9	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
H1N1 influenza
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningitis cryptococcal
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	2 / 2	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Streptococcal urinary tract infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tubo-ovarian abscess
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal abscess
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arteriovenous fistula site infection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blastomycosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus gastrointestinal infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Folliculitis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lymph node tuberculosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ovarian abscess
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomonas infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Progressive multifocal leukoencephalopathy
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psoas abscess
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	8 / 215 (3.72%)	9 / 219 (4.11%)	6 / 226 (2.65%)
occurrences causally related to treatment / all	3 / 8	3 / 11	2 / 7
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1
West Nile viral infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Abdominal wall abscess
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 2	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Labyrinthitis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malaria
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Polyomavirus-associated nephropathy
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 1	0 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Septic shock
subjects affected / exposed	3 / 215 (1.40%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 3	0 / 2	0 / 2
deaths causally related to treatment / all	1 / 2	0 / 1	0 / 2
Sinusitis
subjects affected / exposed	0 / 215 (0.00%)	4 / 219 (1.83%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	2 / 4	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	5 / 215 (2.33%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	2 / 6	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abscess
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus colitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parvovirus infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	2 / 215 (0.93%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 2	1 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	3 / 215 (1.40%)	2 / 219 (0.91%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	2 / 3	2 / 2	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Candida infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cryptococcosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Cytomegalovirus hepatitis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gangrene
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic cyst infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Necrotising fasciitis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis bacterial
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	17 / 215 (7.91%)	9 / 219 (4.11%)	14 / 226 (6.19%)
occurrences causally related to treatment / all	10 / 22	9 / 12	8 / 17
deaths causally related to treatment / all	1 / 5	0 / 0	0 / 1
Strongyloidiasis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	32 / 215 (14.88%)	21 / 219 (9.59%)	26 / 226 (11.50%)
occurrences causally related to treatment / all	15 / 41	11 / 26	5 / 29
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	3 / 215 (1.40%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	3 / 10	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bursitis infective
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus viraemia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal viral infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Parasitic encephalitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Pyelonephritis
subjects affected / exposed	9 / 215 (4.19%)	8 / 219 (3.65%)	9 / 226 (3.98%)
occurrences causally related to treatment / all	6 / 11	6 / 14	2 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyelonephritis viral
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Streptococcal sepsis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound sepsis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BK virus infection
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial diarrhoea
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial pyelonephritis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchopulmonary aspergillosis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Clostridium difficile infection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chest wall abscess
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus duodenitis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus gastroenteritis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	8 / 215 (3.72%)	16 / 219 (7.31%)	13 / 226 (5.75%)
occurrences causally related to treatment / all	6 / 12	12 / 21	10 / 14
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Cytomegalovirus enteritis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infected skin ulcer
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 0	1 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orchitis
subjects affected / exposed	1 / 215 (0.47%)	1 / 219 (0.46%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	2 / 2	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia cytomegaloviral
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
Pertussis
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia legionella
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis syndrome
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sialoadenitis
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	4 / 215 (1.86%)	3 / 219 (1.37%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 4	1 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	2 / 215 (0.93%)	1 / 219 (0.46%)	4 / 226 (1.77%)
occurrences causally related to treatment / all	0 / 2	0 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	2 / 215 (0.93%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 215 (0.00%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	5 / 215 (2.33%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	2 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malnutrition
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acidosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 215 (0.00%)	1 / 219 (0.46%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	6 / 215 (2.79%)	5 / 219 (2.28%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	1 / 6	1 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fluid overload
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	1 / 215 (0.47%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gout
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	3 / 215 (1.40%)	1 / 219 (0.46%)	2 / 226 (0.88%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	4 / 215 (1.86%)	2 / 219 (0.91%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	4 / 5	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	3 / 226 (1.33%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	0 / 215 (0.00%)	0 / 219 (0.00%)	1 / 226 (0.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 215 (0.47%)	0 / 219 (0.00%)	0 / 226 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cyclosporine	Belatacept - MI	Belatacept - LI
Total subjects affected by non serious adverse events
subjects affected / exposed	213 / 215 (99.07%)	216 / 219 (98.63%)	222 / 226 (98.23%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	15 / 215 (6.98%)	14 / 219 (6.39%)	9 / 226 (3.98%)
occurrences all number	32	23	19
Vascular disorders
Haematoma
subjects affected / exposed	16 / 215 (7.44%)	12 / 219 (5.48%)	9 / 226 (3.98%)
occurrences all number	29	20	22
Hypertension
subjects affected / exposed	82 / 215 (38.14%)	70 / 219 (31.96%)	87 / 226 (38.50%)
occurrences all number	186	174	197
Hypotension
subjects affected / exposed	31 / 215 (14.42%)	45 / 219 (20.55%)	36 / 226 (15.93%)
occurrences all number	51	72	57
General disorders and administration site conditions
Oedema
subjects affected / exposed	25 / 215 (11.63%)	13 / 219 (5.94%)	11 / 226 (4.87%)
occurrences all number	53	23	22
Chills
subjects affected / exposed	10 / 215 (4.65%)	9 / 219 (4.11%)	15 / 226 (6.64%)
occurrences all number	12	13	18
Oedema peripheral
subjects affected / exposed	87 / 215 (40.47%)	64 / 219 (29.22%)	70 / 226 (30.97%)
occurrences all number	283	171	197
Pain
subjects affected / exposed	14 / 215 (6.51%)	20 / 219 (9.13%)	14 / 226 (6.19%)
occurrences all number	24	35	21
Pyrexia
subjects affected / exposed	56 / 215 (26.05%)	61 / 219 (27.85%)	68 / 226 (30.09%)
occurrences all number	92	153	113
Asthenia
subjects affected / exposed	21 / 215 (9.77%)	16 / 219 (7.31%)	27 / 226 (11.95%)
occurrences all number	38	24	39
Chest pain
subjects affected / exposed	21 / 215 (9.77%)	22 / 219 (10.05%)	17 / 226 (7.52%)
occurrences all number	40	39	32
Fatigue
subjects affected / exposed	32 / 215 (14.88%)	22 / 219 (10.05%)	27 / 226 (11.95%)
occurrences all number	63	50	65
Peripheral swelling
subjects affected / exposed	9 / 215 (4.19%)	12 / 219 (5.48%)	8 / 226 (3.54%)
occurrences all number	21	31	16
Immune system disorders
Chronic allograft nephropathy
subjects affected / exposed	21 / 215 (9.77%)	5 / 219 (2.28%)	4 / 226 (1.77%)
occurrences all number	23	8	4
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	14 / 215 (6.51%)	10 / 219 (4.57%)	8 / 226 (3.54%)
occurrences all number	26	12	21
Respiratory, thoracic and mediastinal disorders
Productive cough
subjects affected / exposed	9 / 215 (4.19%)	10 / 219 (4.57%)	15 / 226 (6.64%)
occurrences all number	17	20	35
Cough
subjects affected / exposed	57 / 215 (26.51%)	69 / 219 (31.51%)	81 / 226 (35.84%)
occurrences all number	174	226	213
Dyspnoea
subjects affected / exposed	36 / 215 (16.74%)	16 / 219 (7.31%)	18 / 226 (7.96%)
occurrences all number	63	37	32
Rhinorrhoea
subjects affected / exposed	10 / 215 (4.65%)	11 / 219 (5.02%)	13 / 226 (5.75%)
occurrences all number	26	25	30
Oropharyngeal pain
subjects affected / exposed	14 / 215 (6.51%)	19 / 219 (8.68%)	28 / 226 (12.39%)
occurrences all number	26	33	45
Nasal congestion
subjects affected / exposed	4 / 215 (1.86%)	12 / 219 (5.48%)	11 / 226 (4.87%)
occurrences all number	7	22	24
Psychiatric disorders
Depression
subjects affected / exposed	18 / 215 (8.37%)	26 / 219 (11.87%)	17 / 226 (7.52%)
occurrences all number	23	38	26
Insomnia
subjects affected / exposed	38 / 215 (17.67%)	42 / 219 (19.18%)	39 / 226 (17.26%)
occurrences all number	73	112	71
Anxiety
subjects affected / exposed	27 / 215 (12.56%)	27 / 219 (12.33%)	26 / 226 (11.50%)
occurrences all number	38	45	53
Investigations
Weight increased
subjects affected / exposed	24 / 215 (11.16%)	27 / 219 (12.33%)	24 / 226 (10.62%)
occurrences all number	41	51	43
C-reactive protein increased
subjects affected / exposed	11 / 215 (5.12%)	12 / 219 (5.48%)	10 / 226 (4.42%)
occurrences all number	23	52	25
Weight decreased
subjects affected / exposed	8 / 215 (3.72%)	27 / 219 (12.33%)	22 / 226 (9.73%)
occurrences all number	13	62	43
Blood creatinine increased
subjects affected / exposed	53 / 215 (24.65%)	26 / 219 (11.87%)	25 / 226 (11.06%)
occurrences all number	129	60	53
Injury, poisoning and procedural complications
Delayed graft function
subjects affected / exposed	28 / 215 (13.02%)	22 / 219 (10.05%)	26 / 226 (11.50%)
occurrences all number	49	43	47
Transplant dysfunction
subjects affected / exposed	12 / 215 (5.58%)	5 / 219 (2.28%)	7 / 226 (3.10%)
occurrences all number	22	7	10
Contusion
subjects affected / exposed	8 / 215 (3.72%)	11 / 219 (5.02%)	8 / 226 (3.54%)
occurrences all number	14	35	21
Fall
subjects affected / exposed	16 / 215 (7.44%)	10 / 219 (4.57%)	11 / 226 (4.87%)
occurrences all number	25	19	18
Incision site pain
subjects affected / exposed	38 / 215 (17.67%)	33 / 219 (15.07%)	30 / 226 (13.27%)
occurrences all number	71	68	57
Complications of transplanted kidney
subjects affected / exposed	13 / 215 (6.05%)	7 / 219 (3.20%)	10 / 226 (4.42%)
occurrences all number	19	11	19
Complications of transplant surgery
subjects affected / exposed	9 / 215 (4.19%)	11 / 219 (5.02%)	7 / 226 (3.10%)
occurrences all number	12	17	12
Procedural pain
subjects affected / exposed	40 / 215 (18.60%)	41 / 219 (18.72%)	40 / 226 (17.70%)
occurrences all number	85	79	91
Ligament sprain
subjects affected / exposed	7 / 215 (3.26%)	12 / 219 (5.48%)	4 / 226 (1.77%)
occurrences all number	12	20	7
Toxicity to various agents
subjects affected / exposed	27 / 215 (12.56%)	2 / 219 (0.91%)	3 / 226 (1.33%)
occurrences all number	37	2	4
Cardiac disorders
Bradycardia
subjects affected / exposed	13 / 215 (6.05%)	8 / 219 (3.65%)	9 / 226 (3.98%)
occurrences all number	21	10	14
Tachycardia
subjects affected / exposed	23 / 215 (10.70%)	19 / 219 (8.68%)	12 / 226 (5.31%)
occurrences all number	43	31	18
Nervous system disorders
Headache
subjects affected / exposed	46 / 215 (21.40%)	65 / 219 (29.68%)	75 / 226 (33.19%)
occurrences all number	114	151	177
Dizziness
subjects affected / exposed	32 / 215 (14.88%)	24 / 219 (10.96%)	25 / 226 (11.06%)
occurrences all number	74	40	57
Hypoaesthesia
subjects affected / exposed	7 / 215 (3.26%)	12 / 219 (5.48%)	19 / 226 (8.41%)
occurrences all number	10	22	31
Paraesthesia
subjects affected / exposed	19 / 215 (8.84%)	7 / 219 (3.20%)	18 / 226 (7.96%)
occurrences all number	33	12	35
Tremor
subjects affected / exposed	43 / 215 (20.00%)	19 / 219 (8.68%)	19 / 226 (8.41%)
occurrences all number	103	28	37
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	37 / 215 (17.21%)	40 / 219 (18.26%)	48 / 226 (21.24%)
occurrences all number	84	100	101
Polycythaemia
subjects affected / exposed	11 / 215 (5.12%)	14 / 219 (6.39%)	17 / 226 (7.52%)
occurrences all number	16	38	46
Anaemia
subjects affected / exposed	86 / 215 (40.00%)	85 / 219 (38.81%)	92 / 226 (40.71%)
occurrences all number	217	181	253
Leukocytosis
subjects affected / exposed	9 / 215 (4.19%)	10 / 219 (4.57%)	16 / 226 (7.08%)
occurrences all number	15	21	32
Neutropenia
subjects affected / exposed	10 / 215 (4.65%)	9 / 219 (4.11%)	14 / 226 (6.19%)
occurrences all number	20	16	26
Thrombocytopenia
subjects affected / exposed	20 / 215 (9.30%)	16 / 219 (7.31%)	9 / 226 (3.98%)
occurrences all number	33	25	20
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	7 / 215 (3.26%)	5 / 219 (2.28%)	12 / 226 (5.31%)
occurrences all number	11	7	17
Ear pain
subjects affected / exposed	3 / 215 (1.40%)	5 / 219 (2.28%)	13 / 226 (5.75%)
occurrences all number	4	9	27
Eye disorders
Cataract
subjects affected / exposed	11 / 215 (5.12%)	10 / 219 (4.57%)	7 / 226 (3.10%)
occurrences all number	23	13	12
Gastrointestinal disorders
Gastrooesophageal reflux disease
subjects affected / exposed	13 / 215 (6.05%)	11 / 219 (5.02%)	19 / 226 (8.41%)
occurrences all number	18	18	45
Nausea
subjects affected / exposed	70 / 215 (32.56%)	59 / 219 (26.94%)	62 / 226 (27.43%)
occurrences all number	187	128	150
Vomiting
subjects affected / exposed	46 / 215 (21.40%)	45 / 219 (20.55%)	55 / 226 (24.34%)
occurrences all number	96	93	102
Flatulence
subjects affected / exposed	11 / 215 (5.12%)	9 / 219 (4.11%)	16 / 226 (7.08%)
occurrences all number	14	14	26
Gingival hyperplasia
subjects affected / exposed	18 / 215 (8.37%)	2 / 219 (0.91%)	0 / 226 (0.00%)
occurrences all number	31	4	0
Abdominal discomfort
subjects affected / exposed	11 / 215 (5.12%)	8 / 219 (3.65%)	7 / 226 (3.10%)
occurrences all number	19	14	15
Abdominal pain upper
subjects affected / exposed	24 / 215 (11.16%)	19 / 219 (8.68%)	22 / 226 (9.73%)
occurrences all number	37	49	36
Constipation
subjects affected / exposed	68 / 215 (31.63%)	65 / 219 (29.68%)	83 / 226 (36.73%)
occurrences all number	147	137	162
Dyspepsia
subjects affected / exposed	26 / 215 (12.09%)	20 / 219 (9.13%)	35 / 226 (15.49%)
occurrences all number	41	32	63
Abdominal pain
subjects affected / exposed	40 / 215 (18.60%)	47 / 219 (21.46%)	48 / 226 (21.24%)
occurrences all number	88	100	89
Abdominal pain lower
subjects affected / exposed	6 / 215 (2.79%)	13 / 219 (5.94%)	13 / 226 (5.75%)
occurrences all number	17	27	17
Diarrhoea
subjects affected / exposed	92 / 215 (42.79%)	118 / 219 (53.88%)	115 / 226 (50.88%)
occurrences all number	228	374	384
Haemorrhoids
subjects affected / exposed	15 / 215 (6.98%)	14 / 219 (6.39%)	19 / 226 (8.41%)
occurrences all number	21	22	88
Mouth ulceration
subjects affected / exposed	3 / 215 (1.40%)	11 / 219 (5.02%)	7 / 226 (3.10%)
occurrences all number	5	33	18
Abdominal distension
subjects affected / exposed	17 / 215 (7.91%)	16 / 219 (7.31%)	15 / 226 (6.64%)
occurrences all number	27	26	29
Aphthous ulcer
subjects affected / exposed	5 / 215 (2.33%)	13 / 219 (5.94%)	16 / 226 (7.08%)
occurrences all number	15	35	44
Gastritis
subjects affected / exposed	12 / 215 (5.58%)	11 / 219 (5.02%)	14 / 226 (6.19%)
occurrences all number	23	18	26
Skin and subcutaneous tissue disorders
Skin lesion
subjects affected / exposed	15 / 215 (6.98%)	24 / 219 (10.96%)	22 / 226 (9.73%)
occurrences all number	31	57	45
Acne
subjects affected / exposed	31 / 215 (14.42%)	23 / 219 (10.50%)	22 / 226 (9.73%)
occurrences all number	65	45	57
Alopecia
subjects affected / exposed	8 / 215 (3.72%)	16 / 219 (7.31%)	19 / 226 (8.41%)
occurrences all number	10	29	45
Night sweats
subjects affected / exposed	6 / 215 (2.79%)	12 / 219 (5.48%)	11 / 226 (4.87%)
occurrences all number	10	18	17
Pruritus
subjects affected / exposed	17 / 215 (7.91%)	15 / 219 (6.85%)	17 / 226 (7.52%)
occurrences all number	21	30	21
Hypertrichosis
subjects affected / exposed	11 / 215 (5.12%)	4 / 219 (1.83%)	0 / 226 (0.00%)
occurrences all number	17	5	0
Hyperhidrosis
subjects affected / exposed	6 / 215 (2.79%)	9 / 219 (4.11%)	12 / 226 (5.31%)
occurrences all number	8	11	18
Rash
subjects affected / exposed	15 / 215 (6.98%)	20 / 219 (9.13%)	22 / 226 (9.73%)
occurrences all number	32	34	38
Renal and urinary disorders
Dysuria
subjects affected / exposed	34 / 215 (15.81%)	34 / 219 (15.53%)	26 / 226 (11.50%)
occurrences all number	57	59	42
Haematuria
subjects affected / exposed	41 / 215 (19.07%)	33 / 219 (15.07%)	39 / 226 (17.26%)
occurrences all number	101	69	66
Leukocyturia
subjects affected / exposed	9 / 215 (4.19%)	6 / 219 (2.74%)	13 / 226 (5.75%)
occurrences all number	21	25	26
Renal impairment
subjects affected / exposed	14 / 215 (6.51%)	7 / 219 (3.20%)	10 / 226 (4.42%)
occurrences all number	22	12	20
Renal tubular necrosis
subjects affected / exposed	19 / 215 (8.84%)	20 / 219 (9.13%)	17 / 226 (7.52%)
occurrences all number	29	27	32
Proteinuria
subjects affected / exposed	30 / 215 (13.95%)	30 / 219 (13.70%)	41 / 226 (18.14%)
occurrences all number	57	98	95
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	33 / 215 (15.35%)	36 / 219 (16.44%)	40 / 226 (17.70%)
occurrences all number	96	106	79
Osteoarthritis
subjects affected / exposed	7 / 215 (3.26%)	14 / 219 (6.39%)	9 / 226 (3.98%)
occurrences all number	9	23	17
Osteoporosis
subjects affected / exposed	6 / 215 (2.79%)	8 / 219 (3.65%)	15 / 226 (6.64%)
occurrences all number	6	44	18
Arthralgia
subjects affected / exposed	37 / 215 (17.21%)	51 / 219 (23.29%)	54 / 226 (23.89%)
occurrences all number	99	130	116
Myalgia
subjects affected / exposed	17 / 215 (7.91%)	19 / 219 (8.68%)	27 / 226 (11.95%)
occurrences all number	29	27	55
Osteopenia
subjects affected / exposed	13 / 215 (6.05%)	12 / 219 (5.48%)	14 / 226 (6.19%)
occurrences all number	21	13	18
Musculoskeletal pain
subjects affected / exposed	12 / 215 (5.58%)	17 / 219 (7.76%)	17 / 226 (7.52%)
occurrences all number	27	30	30
Back pain
subjects affected / exposed	38 / 215 (17.67%)	47 / 219 (21.46%)	44 / 226 (19.47%)
occurrences all number	63	99	75
Muscular weakness
subjects affected / exposed	14 / 215 (6.51%)	4 / 219 (1.83%)	8 / 226 (3.54%)
occurrences all number	21	6	10
Muscle spasms
subjects affected / exposed	17 / 215 (7.91%)	16 / 219 (7.31%)	11 / 226 (4.87%)
occurrences all number	36	27	23
Infections and infestations
Fungal skin infection
subjects affected / exposed	9 / 215 (4.19%)	10 / 219 (4.57%)	16 / 226 (7.08%)
occurrences all number	20	23	29
Gastroenteritis
subjects affected / exposed	20 / 215 (9.30%)	25 / 219 (11.42%)	19 / 226 (8.41%)
occurrences all number	24	39	34
Conjunctivitis
subjects affected / exposed	9 / 215 (4.19%)	12 / 219 (5.48%)	11 / 226 (4.87%)
occurrences all number	17	22	18
Oral herpes
subjects affected / exposed	12 / 215 (5.58%)	16 / 219 (7.31%)	22 / 226 (9.73%)
occurrences all number	22	40	51
Onychomycosis
subjects affected / exposed	10 / 215 (4.65%)	15 / 219 (6.85%)	16 / 226 (7.08%)
occurrences all number	33	29	36
Bronchitis
subjects affected / exposed	21 / 215 (9.77%)	22 / 219 (10.05%)	29 / 226 (12.83%)
occurrences all number	47	51	69
Herpes zoster
subjects affected / exposed	19 / 215 (8.84%)	20 / 219 (9.13%)	14 / 226 (6.19%)
occurrences all number	34	40	26
Sinusitis
subjects affected / exposed	18 / 215 (8.37%)	17 / 219 (7.76%)	24 / 226 (10.62%)
occurrences all number	37	30	56
Tinea versicolour
subjects affected / exposed	15 / 215 (6.98%)	6 / 219 (2.74%)	11 / 226 (4.87%)
occurrences all number	24	12	26
Upper respiratory tract infection
subjects affected / exposed	52 / 215 (24.19%)	60 / 219 (27.40%)	56 / 226 (24.78%)
occurrences all number	144	184	163
Pharyngitis
subjects affected / exposed	18 / 215 (8.37%)	17 / 219 (7.76%)	22 / 226 (9.73%)
occurrences all number	43	53	52
Candida infection
subjects affected / exposed	4 / 215 (1.86%)	11 / 219 (5.02%)	8 / 226 (3.54%)
occurrences all number	8	19	16
Influenza
subjects affected / exposed	27 / 215 (12.56%)	37 / 219 (16.89%)	40 / 226 (17.70%)
occurrences all number	99	104	113
Nasopharyngitis
subjects affected / exposed	49 / 215 (22.79%)	49 / 219 (22.37%)	39 / 226 (17.26%)
occurrences all number	149	117	130
Urinary tract infection
subjects affected / exposed	77 / 215 (35.81%)	71 / 219 (32.42%)	91 / 226 (40.27%)
occurrences all number	271	432	378
Pneumonia
subjects affected / exposed	8 / 215 (3.72%)	11 / 219 (5.02%)	14 / 226 (6.19%)
occurrences all number	11	21	20
Oral candidiasis
subjects affected / exposed	14 / 215 (6.51%)	19 / 219 (8.68%)	11 / 226 (4.87%)
occurrences all number	27	57	23
BK virus infection
subjects affected / exposed	11 / 215 (5.12%)	13 / 219 (5.94%)	9 / 226 (3.98%)
occurrences all number	15	22	14
Cytomegalovirus infection
subjects affected / exposed	19 / 215 (8.84%)	10 / 219 (4.57%)	13 / 226 (5.75%)
occurrences all number	38	32	38
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	44 / 215 (20.47%)	18 / 219 (8.22%)	41 / 226 (18.14%)
occurrences all number	102	31	64
Hypertriglyceridaemia
subjects affected / exposed	11 / 215 (5.12%)	15 / 219 (6.85%)	6 / 226 (2.65%)
occurrences all number	18	67	9
Hypoglycaemia
subjects affected / exposed	18 / 215 (8.37%)	13 / 219 (5.94%)	15 / 226 (6.64%)
occurrences all number	39	19	26
Hypocalcaemia
subjects affected / exposed	25 / 215 (11.63%)	17 / 219 (7.76%)	27 / 226 (11.95%)
occurrences all number	59	35	45
Hypokalaemia
subjects affected / exposed	28 / 215 (13.02%)	48 / 219 (21.92%)	49 / 226 (21.68%)
occurrences all number	73	108	107
Hyponatraemia
subjects affected / exposed	12 / 215 (5.58%)	6 / 219 (2.74%)	7 / 226 (3.10%)
occurrences all number	26	8	12
Metabolic acidosis
subjects affected / exposed	19 / 215 (8.84%)	13 / 219 (5.94%)	8 / 226 (3.54%)
occurrences all number	28	17	13
Vitamin D deficiency
subjects affected / exposed	9 / 215 (4.19%)	17 / 219 (7.76%)	21 / 226 (9.29%)
occurrences all number	16	27	30
Hyperglycaemia
subjects affected / exposed	42 / 215 (19.53%)	42 / 219 (19.18%)	38 / 226 (16.81%)
occurrences all number	78	65	72
Hypercholesterolaemia
subjects affected / exposed	26 / 215 (12.09%)	34 / 219 (15.53%)	31 / 226 (13.72%)
occurrences all number	53	90	62
Hypomagnesaemia
subjects affected / exposed	24 / 215 (11.16%)	18 / 219 (8.22%)	17 / 226 (7.52%)
occurrences all number	53	29	32
Dehydration
subjects affected / exposed	15 / 215 (6.98%)	6 / 219 (2.74%)	11 / 226 (4.87%)
occurrences all number	20	8	18
Hypophosphataemia
subjects affected / exposed	33 / 215 (15.35%)	36 / 219 (16.44%)	51 / 226 (22.57%)
occurrences all number	75	80	103
Decreased appetite
subjects affected / exposed	13 / 215 (6.05%)	13 / 219 (5.94%)	23 / 226 (10.18%)
occurrences all number	26	25	46
Dyslipidaemia
subjects affected / exposed	70 / 215 (32.56%)	62 / 219 (28.31%)	59 / 226 (26.11%)
occurrences all number	276	173	186
Gout
subjects affected / exposed	11 / 215 (5.12%)	2 / 219 (0.91%)	10 / 226 (4.42%)
occurrences all number	19	4	25
Diabetes mellitus
subjects affected / exposed	15 / 215 (6.98%)	23 / 219 (10.50%)	19 / 226 (8.41%)
occurrences all number	30	72	28
Hypercalcaemia
subjects affected / exposed	13 / 215 (6.05%)	16 / 219 (7.31%)	16 / 226 (7.08%)
occurrences all number	29	34	53
Iron deficiency
subjects affected / exposed	8 / 215 (3.72%)	11 / 219 (5.02%)	11 / 226 (4.87%)
occurrences all number	17	27	32
Hyperlipidaemia
subjects affected / exposed	20 / 215 (9.30%)	19 / 219 (8.68%)	19 / 226 (8.41%)
occurrences all number	27	35	27
Hyperuricaemia
subjects affected / exposed	36 / 215 (16.74%)	8 / 219 (3.65%)	11 / 226 (4.87%)
occurrences all number	87	15	22

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Were there any global substantial amendments to the protocol? Yes

08 Mar 2007

• Changed statistical methodology, • Changed pharmacokinetic sampling regimen, • Changed exclusion criterion for tuberculosis infection, • Clarified Cytomegalovirus prophylaxis regimen, • Added ATG-Fresenius-S to list of permitted polyclonal anti lymphocyte preparations, • Extended the baseline mammogram window, • Clarified performance of baseline biopsy, • Clarified hepatitis B and C and HIV exclusion criterion. • Changed administration of basiliximab.

21 Dec 2007

• Addition of the 250 mg/vial of Belatacept to the list of investigational products, • Addition of long-term extension phase, extending the study two years, • Additional information on contraception use for women of child bearing potential with regard to mycophenolate mofetil (MMF).

18 Oct 2010

• Continuance of long-term extension, • Addition of immunogenicity assessments after discontinuation, • Discontinuation of Quality of Life Short Form-36 (SF-36) after year 5, month 60.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent of Subjects Surviving with a Functioning Graft by Month 12

Primary: Percent of Subjects Surviving with a Functioning Graft by Month 12

Primary: Percent of Subjects with a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or with a Decrease in mGFR Greater Than or Equal to 10 mL/min/1.73m^2 From Month 3 to Month 12

Primary: Percent of Subjects with a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or with a Decrease in mGFR Greater Than or Equal to 10 mL/min/1.73m^2 From Month 3 to Month 12

Primary: Percent of Subjects Experiencing Acute Rejection (AR) Post-transplant by Month 12

Primary: Percent of Subjects Experiencing Acute Rejection (AR) Post-transplant by Month 12

Secondary: Mean Value of the Measured Glomerular Filtration Rate (mGFR)

Secondary: Mean Value of the Measured Glomerular Filtration Rate (mGFR)

Secondary: Percent of Subjects with Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

Secondary: Percent of Subjects with Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

Secondary: Number of Subjects With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

Secondary: Number of Subjects With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

Secondary: Number of Subjects with Adverse Events of Special Interest by Month 84

Secondary: Number of Subjects with Adverse Events of Special Interest by Month 84

Secondary: Mean Blood Pressure at Month 84

Secondary: Mean Blood Pressure at Month 84

Secondary: Number of Subjects Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36

Secondary: Number of Subjects Meeting Marked Laboratory Abnormality Criteria Post-transplant by Month 36

Secondary: Percent of Subjects With Development of Anti-Donor HLA Positive Antibodies by Month 84

Secondary: Percent of Subjects With Development of Anti-Donor HLA Positive Antibodies by Month 84

Secondary: Mean Change of the Measured Glomerular Filtration Rate (mGFR) from Month 3 to Month 12 and from Month 3 to Month 24

Secondary: Mean Change of the Measured Glomerular Filtration Rate (mGFR) from Month 3 to Month 12 and from Month 3 to Month 24

Secondary: Percent of Subjects With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/min/1.73m^2 from Month 3 to Month 12

Secondary: Percent of Subjects With a Decrease in Measured Glomerular Filtration Rate (mGFR) Greater Than or Equal to 10mL/min/1.73m^2 from Month 3 to Month 12

Secondary: Percent of Subjects with a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/min/1.73 m^2 at Month 12

Secondary: Percent of Subjects with a Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/min/1.73 m^2 at Month 12

Secondary: Mean Value of the Calculated Glomerular Filtration Rate (cGFR) with Imputation

Secondary: Mean Value of the Calculated Glomerular Filtration Rate (cGFR) with Imputation

Secondary: Mean Change in Calculated Glomerular Filtration Rate (cGFR) from Month 6 to Month 12

Secondary: Mean Change in Calculated Glomerular Filtration Rate (cGFR) from Month 6 to Month 12

Secondary: Percent of Subjects with Incidence of New Onset Diabetes Mellitus by Month 36

Secondary: Percent of Subjects with Incidence of New Onset Diabetes Mellitus by Month 36

Secondary: Percent of Subjects Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36

Secondary: Percent of Subjects Using At Least One Anti-Hypertensive Medication to Control Hypertension at Month 36

Secondary: Percent of Subjects with Incidence of Hypertension Post-Transplantation at Month 12

Secondary: Percent of Subjects with Incidence of Hypertension Post-Transplantation at Month 12

Secondary: Percent of Subjects With Prevalence of Hypertension Post-Transplantation at Month 12

Secondary: Percent of Subjects With Prevalence of Hypertension Post-Transplantation at Month 12

Secondary: Mean Systolic Blood Pressure and Diastolic Blood Pressure

Secondary: Mean Systolic Blood Pressure and Diastolic Blood Pressure

Secondary: Percent of Subjects at Baseline with Controlled Hypertension Post Transplantation by Month 12

Secondary: Percent of Subjects at Baseline with Controlled Hypertension Post Transplantation by Month 12

Secondary: Percent of Subjects with Prevalence of Controlled Hypertension at Month 12

Secondary: Percent of Subjects with Prevalence of Controlled Hypertension at Month 12

Secondary: Percent of Non-dyslipidemic Subjects With Incidence of Dyslipidemia Post-Transplantation by Month 12

Secondary: Percent of Non-dyslipidemic Subjects With Incidence of Dyslipidemia Post-Transplantation by Month 12

Secondary: Percent of Subjects With Prevalence of Dyslipidemia at Month 12

Secondary: Percent of Subjects With Prevalence of Dyslipidemia at Month 12

Secondary: Percent of Subjects With Controlled Dyslipidemia at Month 12

Secondary: Percent of Subjects With Controlled Dyslipidemia at Month 12

Secondary: Number of Subjects With Antihyperlipidemic Medication by Intensity Level

Secondary: Number of Subjects With Antihyperlipidemic Medication by Intensity Level

Secondary: Percent of Subjects Using At Least One Anti-Hyperlipidemic Medication

Secondary: Percent of Subjects Using At Least One Anti-Hyperlipidemic Medication

Secondary: Mean Value of Lipid Parameters

Secondary: Mean Value of Lipid Parameters

Secondary: Percent of Subjects with Prevalence of Acute Rejection (AR) by Month 36

Secondary: Percent of Subjects with Prevalence of Acute Rejection (AR) by Month 36

Secondary: Number of Subjects with Acute Rejection (AR) Post-transplant in Terms of Severity using Banff Grades by Month 36

Secondary: Number of Subjects with Acute Rejection (AR) Post-transplant in Terms of Severity using Banff Grades by Month 36

Secondary: Percent of Subjects Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12

Secondary: Percent of Subjects Using Polyclonal Antilymphocyte Preparations for Impaired Renal Function and Anticipated Delayed Graft Function by Month 12

Secondary: Percent of Subjects Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36

Secondary: Percent of Subjects Using Lymphocyte Depleting Therapy (LDT) for the Initial Treatment of Acute Rejection (AR) by Month 36

Secondary: Percent of Subjects with Corticosteroid resistant Acute Rejection (AR) by Month 36

Secondary: Percent of Subjects with Corticosteroid resistant Acute Rejection (AR) by Month 36

Secondary: Number of Subjects Who Recovered Completely from an Episode of Acute Rejection (AR) by Month 12

Secondary: Number of Subjects Who Recovered Completely from an Episode of Acute Rejection (AR) by Month 12

Secondary: Percent of Subjects with Subclinical Rejection at Month 12

Secondary: Percent of Subjects with Subclinical Rejection at Month 12

Clinical Trial Results:
Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT)