Trial Outcomes & Findings for Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients (NCT NCT01114529)

Last Updated: 2017-05-30

Results Overview

Assessment of renal function by comparing change from randomization to Month 12 in eGFR (MDRD4) between treatment arms (Full analysis set). Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR \[mL/min/1.73m˄2\] = 186.3\*(C˄-1.154)\*(A˄-0.203)\*G\*R. DEFINITIONS: C = serum concentration of creatinine \[mg/dL\]; A = age \[years\]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

828 participants

Primary outcome timeframe

Month 12

Results posted on

2017-05-30

Participant Flow

Full analysis set (24 month analysis)

Participant milestones

Participant milestones
Measure	Everolimus Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid), and steroids	Standard CNI (CsA) Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid) and steroids
Completed Study Medication at Month 24 STARTED	353	231	125
Completed Study Medication at Month 24 COMPLETED	229	190	93
Completed Study Medication at Month 24 NOT COMPLETED	124	41	32
Completed Study Phase at Month 24 STARTED	353	231	125
Completed Study Phase at Month 24 COMPLETED	313	215	111
Completed Study Phase at Month 24 NOT COMPLETED	40	16	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid), and steroids	Standard CNI (CsA) Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid) and steroids
Completed Study Medication at Month 24 Adverse Event	87	18	17
Completed Study Medication at Month 24 Abnormal laboratory value(s)	6	0	1
Completed Study Medication at Month 24 Abnormal test procedure result(s)	3	0	1
Completed Study Medication at Month 24 Lack of Efficacy	2	1	2
Completed Study Medication at Month 24 Subject's no longer required drug	1	1	1
Completed Study Medication at Month 24 Withdrawal by Subject	18	8	2
Completed Study Medication at Month 24 Lost to Follow-up	1	4	2
Completed Study Medication at Month 24 Administrative problems	2	1	2
Completed Study Medication at Month 24 Death	2	1	2
Completed Study Medication at Month 24 Graft loss	0	2	0
Completed Study Medication at Month 24 Protocol Violation	0	5	2
Completed Study Medication at Month 24 Missing	2	0	0
Completed Study Phase at Month 24 Withdrawal by Subject	18	6	3
Completed Study Phase at Month 24 Lost to Follow-up	10	5	7
Completed Study Phase at Month 24 Death	8	5	4
Completed Study Phase at Month 24 Other	2	0	0
Completed Study Phase at Month 24 Missing	2	0	0

Baseline Characteristics

Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus n=353 Participants Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) n=231 Participants Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid), and steroids	Standard CNI (CsA) n=125 Participants Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid) and steroids	Total n=709 Participants Total of all reporting groups
Age, Continuous	46.0 years STANDARD_DEVIATION 14.4 • n=93 Participants	47.3 years STANDARD_DEVIATION 14.5 • n=4 Participants	45.4 years STANDARD_DEVIATION 15.6 • n=27 Participants	46.2 years STANDARD_DEVIATION 14.8 • n=483 Participants
Sex: Female, Male Female	111 Participants n=93 Participants	71 Participants n=4 Participants	33 Participants n=27 Participants	215 Participants n=483 Participants
Sex: Female, Male Male	242 Participants n=93 Participants	160 Participants n=4 Participants	92 Participants n=27 Participants	494 Participants n=483 Participants
Race/Ethnicity, Customized Caucasian	246 participants 69.7 • n=93 Participants	173 participants 74.9 • n=4 Participants	97 participants 77.6 • n=27 Participants	516 participants n=483 Participants
Race/Ethnicity, Customized Black	4 participants 1.1 • n=93 Participants	5 participants 2.2 • n=4 Participants	0 participants 0 • n=27 Participants	9 participants n=483 Participants
Race/Ethnicity, Customized Asian	66 participants 18.7 • n=93 Participants	41 participants 17.7 • n=4 Participants	20 participants 16.0 • n=27 Participants	127 participants n=483 Participants
Race/Ethnicity, Customized Native American	1 participants 0.3 • n=93 Participants	0 participants 0.0 • n=4 Participants	0 participants 0.0 • n=27 Participants	1 participants n=483 Participants
Race/Ethnicity, Customized Pacific Islander	0 participants 0 • n=93 Participants	1 participants 0.4 • n=4 Participants	1 participants 0.8 • n=27 Participants	2 participants n=483 Participants
Race/Ethnicity, Customized Other	36 participants 10.2 • n=93 Participants	11 participants 4.8 • n=4 Participants	7 participants 5.6 • n=27 Participants	54 participants n=483 Participants

PRIMARY outcome

Timeframe: Month 12

Population: Full Analysis set - observed eGFR values at month 12 (counted the patients with available values)

Outcome measures

Outcome measures
Measure	Everolimus n=327 Participants Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) n=213 Participants Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (CsA) n=116 Participants Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid), and steroids
Estimated Glomerular Filtration Rate (eGFR)	64.1 mL/min/1.73m^2 Standard Deviation 22.31	61.5 mL/min/1.73m^2 Standard Deviation 19.86	58.4 mL/min/1.73m^2 Standard Deviation 19.62

SECONDARY outcome

Timeframe: at 12 months and month 24 post-transplantation

Population: Full Analysis Set

Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)\*, (2) graft loss\*\*, or (3) death . \*A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. \*\*Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted.

Outcome measures

Outcome measures
Measure	Everolimus n=359 Participants Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) n=231 Participants Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (CsA) n=125 Participants Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid), and steroids
Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 Month 12	21 Number of incidence	4 Number of incidence	8 Number of incidence
Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 Month 24	27 Number of incidence	8 Number of incidence	8 Number of incidence

SECONDARY outcome

Timeframe: Randomization, Month 12 and Month 24

Population: Full Analysis Set consists of only patients with triple LVMi values available at randomization, Month 12 and month 24 are included

Evolution of left ventricular mass and hypertrophy were evaluated by left ventricular mass index (LVMi) assessed by echocardiography. LVMi is derived using a standard formula from dimensional measurements on the echocardiogram. Analysis of covariance was applied with treatment, center (as a random effect), and donor type as factors and LVMi at Randomization as covariate.

Outcome measures

Outcome measures
Measure	Everolimus n=180 Participants Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) n=156 Participants Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (CsA) n=75 Participants Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid), and steroids
Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 Randomization	50.30 g/m^2.7 Standard Deviation 11.62	51.08 g/m^2.7 Standard Deviation 14.11	51.13 g/m^2.7 Standard Deviation 12.70
Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 Month 12	49.95 g/m^2.7 Standard Deviation 12.63	48.98 g/m^2.7 Standard Deviation 14.63	50.96 g/m^2.7 Standard Deviation 13.00
Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 Month 24	46.66 g/m^2.7 Standard Deviation 12.19	45.63 g/m^2.7 Standard Deviation 13.50	47.91 g/m^2.7 Standard Deviation 12.71

SECONDARY outcome

Timeframe: at 24 months post-transplantation

Population: Full Analysis Set

(treated BPAR ≥ IB, graft loss or death)A comparison of the incidence rates for the individual components of the composite efficacy endpoint between treatment arms

Outcome measures

Outcome measures
Measure	Everolimus n=353 Participants Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) n=231 Participants Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (CsA) n=125 Participants Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid), and steroids
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Composite failure: tBPAR>=IB, graft loss, death	27 Number of incidence	8 Number of incidence	8 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Composite tBPAR>=IB, graft loss, death, loss f/u	35 Number of incidence	14 Number of incidence	15 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Composite of graft loss or Death	10 Number of incidence	6 Number of incidence	4 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) tBPAR>=IB	18 Number of incidence	3 Number of incidence	5 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Graft loss	4 Number of incidence	2 Number of incidence	2 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Death	8 Number of incidence	5 Number of incidence	4 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Suspected Acute rejection	61 Number of incidence	27 Number of incidence	19 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Subclinical Acute rejection	0 Number of incidence	0 Number of incidence	0 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Acute rejection (AR)	52 Number of incidence	14 Number of incidence	15 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Treated Acute rejection (tAR)	40 Number of incidence	9 Number of incidence	14 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) biopsy proven acute rejection (BPAR)	37 Number of incidence	8 Number of incidence	13 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) treated biopsy proven acute rejection (tBPAR)	32 Number of incidence	7 Number of incidence	13 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) tBPAR=IA	16 Number of incidence	3 Number of incidence	8 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) tBPAR=IB	14 Number of incidence	3 Number of incidence	5 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) tBPAR=IIA	3 Number of incidence	0 Number of incidence	1 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) tBPAR=IIB	2 Number of incidence	0 Number of incidence	0 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) tBPAR=III	0 Number of incidence	0 Number of incidence	0 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Antibody tBPAR	2 Number of incidence	1 Number of incidence	1 Number of incidence
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) Antibody mediated rejection (AMR)	16 Number of incidence	4 Number of incidence	3 Number of incidence

Adverse Events

Everolimus

Serious events: 188 serious events

Other events: 316 other events

Deaths: 0 deaths

Standard CNI (Tac)

Serious events: 118 serious events

Other events: 216 other events

Deaths: 0 deaths

Standard CNI (CsA)

Serious events: 58 serious events

Other events: 103 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1(862)778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing any publications from a single-site are postponed until publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Everolimus n=346 participants at risk Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (Tac) n=238 participants at risk Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid) and steroids	Standard CNI (CsA) n=121 participants at risk Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid) and steroids
Blood and lymphatic system disorders Anaemia	11.8% 41/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.8% 21/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	4.1% 5/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Blood and lymphatic system disorders Leukopenia	13.9% 48/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	14.7% 35/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	9.1% 11/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Gastrointestinal disorders Diarrhoea	22.8% 79/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	23.1% 55/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	10.7% 13/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Gastrointestinal disorders Mouth ulceration	6.9% 24/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	0.84% 2/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	0.83% 1/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Gastrointestinal disorders Nausea	6.1% 21/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.9% 14/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	3.3% 4/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Gastrointestinal disorders Vomiting	6.1% 21/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	3.8% 9/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	2.5% 3/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
General disorders Oedema peripheral	17.3% 60/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.8% 21/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	10.7% 13/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
General disorders Pyrexia	17.9% 62/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.4% 20/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	9.9% 12/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations Nasopharyngitis	9.0% 31/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	9.7% 23/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.3% 10/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations Upper respiratory tract infection	5.8% 20/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.0% 19/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	1.7% 2/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations Urinary tract infection	21.7% 75/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	19.7% 47/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	14.9% 18/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Investigations Blood creatinine increased	8.7% 30/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	10.1% 24/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	16.5% 20/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Metabolism and nutrition disorders Diabetes mellitus	4.3% 15/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.0% 19/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	3.3% 4/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Metabolism and nutrition disorders Dyslipidaemia	7.5% 26/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	4.6% 11/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	3.3% 4/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Metabolism and nutrition disorders Hypercholesterolaemia	11.6% 40/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	6.3% 15/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.8% 7/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Metabolism and nutrition disorders Hyperlipidaemia	4.9% 17/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	4.6% 11/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	7.4% 9/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Metabolism and nutrition disorders Hypokalaemia	6.9% 24/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.5% 13/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	0.83% 1/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Renal and urinary disorders Proteinuria	15.0% 52/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	4.6% 11/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	1.7% 2/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Respiratory, thoracic and mediastinal disorders Cough	8.4% 29/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	6.7% 16/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	2.5% 3/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Skin and subcutaneous tissue disorders Acne	5.5% 19/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	3.4% 8/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	2.5% 3/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Vascular disorders Hypertension	10.1% 35/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	10.1% 24/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	9.9% 12/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations BK virus infection	1.4% 5/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.5% 13/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	4.1% 5/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations Cytomegalovirus infection	3.8% 13/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.5% 13/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	7.4% 9/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations Gastroenteritis	5.8% 20/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	7.6% 18/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	6.6% 8/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Infections and infestations Pneumonia	5.8% 20/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	3.4% 8/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.0% 6/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Immune system disorders Kidney transplant rejection	6.4% 22/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	2.5% 6/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	7.4% 9/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Immune system disorders Transplant rejection	7.5% 26/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	2.9% 7/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	8.3% 10/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Renal and urinary disorders Hematuria	4.3% 15/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	7.6% 18/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	1.7% 2/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Renal and urinary disorders Renal impairment	4.9% 17/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.5% 13/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	5.8% 7/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.5% 19/346 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	4.2% 10/238 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set	0.83% 1/121 • 24 months Incidence of serious adverse events/infections by primary system organ class and preferred tem and treatment- Safety analysis set