Trial Outcomes & Findings for Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients (NCT NCT00622869)

Last Updated: 2013-05-27

Results Overview

Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, they received a graft re-transplant, or they died. The incidence rates of composite efficacy failure were estimated with a Kaplan-Meier product-limit formula.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

719 participants

Primary outcome timeframe

Randomization to Month 12

Results posted on

2013-05-27

Participant Flow

Participant milestones

Participant milestones
Measure	Everolimus + Reduced Tacrolimus Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm Control dose tacrolimus + corticosteroids.
Overall Study STARTED	245	231	243
Overall Study COMPLETED	202	174	204
Overall Study NOT COMPLETED	43	57	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + Reduced Tacrolimus Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm Control dose tacrolimus + corticosteroids.
Overall Study Subject Withdrew Consent	13	17	11
Overall Study Administrative Problems	11	17	13
Overall Study Death	12	15	10
Overall Study Lost to Follow-up	2	4	2
Overall Study Graft Loss	5	3	2
Overall Study Missing	0	1	1

Baseline Characteristics

Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + Reduced Tacrolimus n=245 Participants Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination n=231 Participants Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm n=243 Participants Control dose tacrolimus + corticosteroids.	Total n=719 Participants Total of all reporting groups
Age Continuous	53.6 years STANDARD_DEVIATION 9.2 • n=5 Participants	53.2 years STANDARD_DEVIATION 10.8 • n=7 Participants	54.5 years STANDARD_DEVIATION 8.7 • n=5 Participants	53.8 years STANDARD_DEVIATION 9.6 • n=4 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	67 Participants n=7 Participants	64 Participants n=5 Participants	196 Participants n=4 Participants
Sex: Female, Male Male	180 Participants n=5 Participants	164 Participants n=7 Participants	179 Participants n=5 Participants	523 Participants n=4 Participants

PRIMARY outcome

Timeframe: Randomization to Month 12

Population: Intent-to-treat population: All randomized patients.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Tacrolimus n=245 Participants Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination n=231 Participants Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm n=243 Participants Control dose tacrolimus + corticosteroids.
Incidence Rate of Composite Efficacy Failure From Randomization to Month 12	6.7 Percentage of participants	24.2 Percentage of participants	9.7 Percentage of participants

SECONDARY outcome

Timeframe: Randomization to Month 24

Population: Intent-to-treat population: All randomized patients.

Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. The incidence rates of composite efficacy failure were estimated with a Kaplan-Meier product-limit formula.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Tacrolimus n=245 Participants Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination n=231 Participants Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm n=243 Participants Control dose tacrolimus + corticosteroids.
Incidence Rate of Composite Efficacy Failure From Randomization to Month 24	10.3 Percentage	26.0 Percentage	12.5 Percentage

SECONDARY outcome

Timeframe: Randomization to Month 24

Population: Intent-to-treat population: All randomized patients.

tBPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3, which was treated with anti-rejection therapy. Liver biopsies were collected for all cases of suspected acute rejection preferably within 24 hours, at the latest within 48 hours, whenever clinically possible. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, they received a graft re-transplant, or they died. The incidence rates of tBPAR were estimated with a Kaplan-Meier product-limit formula.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Tacrolimus n=245 Participants Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination n=231 Participants Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm n=243 Participants Control dose tacrolimus + corticosteroids.
Incidence Rate of Treated Biopsy Proven Acute Rejection (tBPAR) at Months 12 and 24 Month 12	3.0 Percentage	18.8 Percentage	7.2 Percentage
Incidence Rate of Treated Biopsy Proven Acute Rejection (tBPAR) at Months 12 and 24 Month 24	4.8 Percentage	19.9 Percentage	7.7 Percentage

SECONDARY outcome

Timeframe: Randomization to Month 24

Population: Intent-to-treat population: All randomized patients.

Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m\^2) = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Tacrolimus n=245 Participants Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids.	Tacrolimus Elimination n=231 Participants Low-dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids.	Tacrolimus Control Arm n=243 Participants Control dose tacrolimus + corticosteroids.
Change in Renal Function From Randomization to Months 12 and 24 Month 12 (N=244, 231, 243)	-2.23 mL/min/1.73m^2 Standard Error 1.54	-1.51 mL/min/1.73m^2 Standard Error 1.58	-10.73 mL/min/1.73m^2 Standard Error 1.54
Change in Renal Function From Randomization to Months 12 and 24 Month 24 (N=245, 231, 243)	-7.94 mL/min/1.73m^2 Standard Error 1.53	-4.19 mL/min/1.73m^2 Standard Error 1.58	-14.60 mL/min/1.73m^2 Standard Error 1.54

Adverse Events

Everolimus + Reduced Tacrolimus

Serious events: 138 serious events

Other events: 218 other events

Deaths: 0 deaths

Tacrolimus Elimination

Serious events: 152 serious events

Other events: 194 other events

Deaths: 0 deaths

Tacrolimus Control Arm

Serious events: 131 serious events

Other events: 205 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778-8300

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 the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Everolimus + Reduced Tacrolimus n=245 participants at risk Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids	Tacrolimus Elimination n=229 participants at risk Low dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids	Tacrolimus Control Arm n=242 participants at risk Control dose tacrolimus + corticosteroids
Blood and lymphatic system disorders Pancytopenia	2.4% 6/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Thrombocytopenia	1.2% 3/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.87% 2/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Anaemia	1.6% 4/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	1.7% 4/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.1% 5/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Anaemia megaloblastic	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Leukocytosis	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Neutropenia	0.82% 2/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Infections and infestations Anal abscess	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Acute coronary syndrome	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Acute myocardial infarction	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.83% 2/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Angina pectoris	0.82% 2/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	1.2% 3/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Angina unstable	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Arteriosclerosis coronary artery	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Atrial fibrillation	0.82% 2/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Atrioventricular block second degree	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Cardiac arrest	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Cardiac failure	0.82% 2/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.83% 2/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Cardiac failure congestive	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Coronary artery disease	1.2% 3/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	1.2% 3/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Myocardial infarction	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Myocardial ischaemia	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Palpitations	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Pericarditis	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Cardiac disorders Tachyarrhythmia	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Congenital, familial and genetic disorders Hepato-lenticular degeneration	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Congenital, familial and genetic disorders Hydrocele	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Ear and labyrinth disorders Acute vestibular syndrome	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Ear and labyrinth disorders Vertigo	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.87% 2/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Eye disorders Glaucoma	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Eye disorders Retinal detachment	0.82% 2/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal hernia	2.0% 5/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	4.8% 11/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.1% 5/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal pain	2.0% 5/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.1% 7/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	1.2% 3/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal pain upper	0.41% 1/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.00% 0/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.41% 1/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Ascites	1.6% 4/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	1.3% 3/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.83% 2/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.

Other adverse events
Measure	Everolimus + Reduced Tacrolimus n=245 participants at risk Low dose tacrolimus (tacrolimus reduced) + everolimus + corticosteroids	Tacrolimus Elimination n=229 participants at risk Low dose tacrolimus (until Month 4, then tacrolimus eliminated) + everolimus + corticosteroids	Tacrolimus Control Arm n=242 participants at risk Control dose tacrolimus + corticosteroids
Skin and subcutaneous tissue disorders Pruritus	5.3% 13/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	4.8% 11/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.5% 6/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Skin and subcutaneous tissue disorders Pruritus generalised	5.3% 13/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.1% 14/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.0% 17/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Vascular disorders Hypertension	20.8% 51/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	15.3% 35/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	17.4% 42/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Anaemia	9.0% 22/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	11.4% 26/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	8.3% 20/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Leukopenia	12.7% 31/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	10.0% 23/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	5.0% 12/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Blood and lymphatic system disorders Thrombocytopenia	6.5% 16/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.4% 17/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.1% 5/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal pain	14.3% 35/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	12.7% 29/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	11.6% 28/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Abdominal pain upper	5.3% 13/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	4.4% 10/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.6% 16/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Constipation	7.3% 18/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.0% 16/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	8.3% 20/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Diarrhoea	22.9% 56/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	24.0% 55/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	24.0% 58/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Nausea	14.7% 36/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	10.0% 23/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	13.6% 33/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Gastrointestinal disorders Vomiting	8.2% 20/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.4% 17/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	8.7% 21/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
General disorders Fatigue	11.0% 27/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.6% 22/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	11.6% 28/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
General disorders Oedema peripheral	20.0% 49/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	18.8% 43/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	12.8% 31/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
General disorders Pyrexia	15.1% 37/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	17.0% 39/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.5% 23/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Hepatobiliary disorders Cholestasis	6.1% 15/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.1% 7/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.9% 7/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Infections and infestations Hepatitis C	10.2% 25/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.4% 17/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	8.7% 21/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Infections and infestations Nasopharyngitis	9.8% 24/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	10.5% 24/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	10.7% 26/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Infections and infestations Urinary tract infection	8.6% 21/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.0% 16/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	4.5% 11/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Injury, poisoning and procedural complications Incisional hernia	7.8% 19/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.9% 9/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.2% 15/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Investigations Blood creatinine increased	2.0% 5/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.6% 6/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.4% 18/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Investigations Hepatic enzyme increased	5.3% 13/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	8.3% 19/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	5.8% 14/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Investigations Liver function test abnormal	6.5% 16/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	10.9% 25/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.5% 23/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Investigations Transaminases increased	5.7% 14/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.9% 9/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.7% 9/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Decreased appetite	6.5% 16/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.6% 6/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.6% 16/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Diabetes mellitus	6.9% 17/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.5% 8/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	5.0% 12/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Hypercholesterolaemia	11.0% 27/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.2% 21/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.7% 9/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Hyperkalaemia	4.9% 12/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.5% 8/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.9% 24/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Hyperlipidaemia	8.6% 21/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	10.5% 24/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.1% 5/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Hypertriglyceridaemia	8.2% 20/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.9% 9/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	1.7% 4/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Hypokalaemia	5.3% 13/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.9% 9/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.7% 9/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Metabolism and nutrition disorders Hypomagnesaemia	7.8% 19/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	2.6% 6/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.0% 17/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Musculoskeletal and connective tissue disorders Arthralgia	8.6% 21/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	5.2% 12/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.5% 23/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Musculoskeletal and connective tissue disorders Back pain	8.2% 20/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	5.7% 13/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	12.0% 29/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Musculoskeletal and connective tissue disorders Muscle spasms	5.7% 14/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.9% 9/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	9.5% 23/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.0% 5/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	0.44% 1/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.2% 15/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Musculoskeletal and connective tissue disorders Pain in extremity	4.1% 10/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.1% 14/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	6.6% 16/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Nervous system disorders Headache	20.8% 51/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	17.5% 40/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	21.9% 53/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Nervous system disorders Tremor	9.4% 23/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	7.4% 17/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	14.9% 36/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.
Psychiatric disorders Depression	6.5% 16/245 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	3.9% 9/229 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.	5.8% 14/242 • Adverse events (AE) were followed until resolution or judged permanent. Serious AEs occurring after transplantation, until 30 days after study medication (SM) discontinuation, or > 4 weeks after study discontinuation if related to SM were reported. Safety population: All patients who received at least 1 dose of randomized study medication. Adverse events up to Month 24 were reported.