Trial Outcomes & Findings for Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients (NCT NCT00895583)

NCT ID: NCT00895583

Last Updated: 2014-09-18

Results Overview

GFR was calculated using the Modified Diet in Renal Disease (MDRD) equation using either serum creatinine traceable to isotope dilution mass spectrometry (IDMS) or serum creatinine not traceable to IDMS.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 254 participants
• Primary outcome timeframe: Baseline, Month 24
• Results posted on: 2014-09-18

Participant Flow

Participant milestones

Measure	Sirolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Overall Study STARTED	131	123
Overall Study COMPLETED	87	111
Overall Study NOT COMPLETED	44	12

Reasons for withdrawal

Measure	Sirolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Overall Study Adverse Event	28	4
Overall Study Death	2	1
Overall Study Physician Decision	3	1
Overall Study Lost to Follow-up	1	3
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	4	2
Overall Study Lack of Efficacy	5	0
Overall Study Other	0	1

Baseline Characteristics

Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients

Baseline characteristics by cohort

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Total n=254 Participants Total of all reporting groups
Age, Continuous	50.7 years STANDARD_DEVIATION 13.03 • n=5 Participants	52.4 years STANDARD_DEVIATION 12.05 • n=7 Participants	51.5 years STANDARD_DEVIATION 12.57 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	46 Participants n=7 Participants	88 Participants n=5 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	77 Participants n=7 Participants	166 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 24

Population: On-Therapy Population (24 Months): all randomized participants who remained on assigned study therapy through 24 months post-transplantation.

GFR was calculated using the Modified Diet in Renal Disease (MDRD) equation using either serum creatinine traceable to isotope dilution mass spectrometry (IDMS) or serum creatinine not traceable to IDMS.

Outcome measures

Measure	Sirolimus n=86 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=109 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Improvement of Greater Than or Equal to [≥]5 Milliliters Per Minute Per 1.73 Square Meters (mL/Min/m^2) in Calculated Glomerular Filtration Rate (GFR) at 24 Months Post-Transplantation (On-Therapy Analysis)	33.7 percentage of participants	42.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: On-Therapy Population (12 Months): all randomized participants who remained on assigned study therapy through 12 months post-transplantation.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.

Outcome measures

Measure	Sirolimus n=109 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=116 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis)	39.4 percentage of participants	44.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: ITT Population: all randomized participants who received at least 1 dose of the assigned therapy after randomization. Missing GFR was imputed as follows: 1) GFR equals (=)0 after graft loss and 2) last observed value prior to missing was carried forward for death (with functioning graft), early termination or skipped assessment.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation (Intent-to-Treat [ITT] Analysis) Month 12	38.2 percentage of participants	42.3 percentage of participants
Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation (Intent-to-Treat [ITT] Analysis) Month 24	33.6 percentage of participants	40.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: ITT Population. Missing GFR was imputed as follows: 1) GFR=0 after graft loss and 2) last observed value prior to missing was carried forward for death (with functioning graft), early termination or skipped assessment.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation Month 12	24.4 percentage of participants	35.8 percentage of participants
Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation Month 24	25.2 percentage of participants	30.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: ITT Population. Missing GFR was imputed as follows: 1) GFR=0 after graft loss and 2) last observed value prior to missing was carried forward for death (with functioning graft), early termination or skipped assessment.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation Month 12	19.8 percentage of participants	23.6 percentage of participants
Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation Month 24	22.1 percentage of participants	22.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 6, 12, 18, and 24

Population: On-Therapy Population: all participants who remained on assigned study therapy up to the point of discontinuation. number (n)=number of participants assessed for the specified parameter at a given visit.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Calculated GFR Using MDRD (On-Therapy Analysis) Baseline (n=131,123)	58.5 mL/min/1.73 m^2 Standard Deviation 14.3	57.4 mL/min/1.73 m^2 Standard Deviation 14.1
Calculated GFR Using MDRD (On-Therapy Analysis) Month 6 (n=125,120)	61.6 mL/min/1.73 m^2 Standard Deviation 14.9	57.6 mL/min/1.73 m^2 Standard Deviation 14.2
Calculated GFR Using MDRD (On-Therapy Analysis) Month 12 (n=109,116)	59.6 mL/min/1.73 m^2 Standard Deviation 16.4	61.3 mL/min/1.73 m^2 Standard Deviation 14.3
Calculated GFR Using MDRD (On-Therapy Analysis) Month 18 (n=99,111)	60.0 mL/min/1.73 m^2 Standard Deviation 15.0	59.8 mL/min/1.73 m^2 Standard Deviation 17.1
Calculated GFR Using MDRD (On-Therapy Analysis) Month 24 (n=86,109)	59.4 mL/min/1.73 m^2 Standard Deviation 18.0	58.4 mL/min/1.73 m^2 Standard Deviation 14.9

SECONDARY outcome

Timeframe: Baseline, Months 6, 12, 18, and 24

Population: On-Therapy Population; n=number of participants assessed for the specified parameter at a given visit.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis) Month 6 (n=125,120)	2.7 mL/min/1.73 m^2 Standard Error 1.1	0.0 mL/min/1.73 m^2 Standard Error 0.8
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis) Month 12 (n=109,116)	1.5 mL/min/1.73 m^2 Standard Error 1.2	3.4 mL/min/1.73 m^2 Standard Error 1.1
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis) Month 18 (n=99,111)	2.2 mL/min/1.73 m^2 Standard Error 1.2	1.5 mL/min/1.73 m^2 Standard Error 1.3
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis) Month 24 (n=86,109)	1.2 mL/min/1.73 m^2 Standard Error 1.6	0.6 mL/min/1.73 m^2 Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: On-Therapy analysis of the slope comprised the data collected from the on-therapy evaluations for all the participants in the ITT population; data collected from participants receiving sirolimus during the first 3 weeks post-randomization for safety monitoring were excluded from the analysis.

GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Timepoints were calculated as study days, relative to the time of randomization of study medication. All available on-therapy values were included. Observed data were multiplied by a scale factor of 365, expressing the slope as an annual change.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)	-0.9 mL/min/1.73 m^2 per year Interval -2.7 to 0.8	0.9 mL/min/1.73 m^2 per year Interval -0.7 to 2.5

SECONDARY outcome

Timeframe: Baseline, Months 6, 12, 18, and 24

Population: On-Therapy Population: all participants who remained on assigned study therapy up to the point of discontinuation. n=number of participants assessed for the specified parameter at a given visit.

Serum creatinine was measured in micromillimoles per liter (mcmol/L). Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Serum Creatinine (On-Therapy Analysis) Baseline (n=131,123)	118.3 mcmol/L Standard Deviation 24.8	117.7 mcmol/L Standard Deviation 27.9
Serum Creatinine (On-Therapy Analysis) Month 6 (n=125,120)	113.9 mcmol/L Standard Deviation 27.6	117.0 mcmol/L Standard Deviation 28.2
Serum Creatinine (On-Therapy Analysis) Month 12 (n=109,116)	119.6 mcmol/L Standard Deviation 37.5	109.4 mcmol/L Standard Deviation 24.6
Serum Creatinine (On-Therapy Analysis) Month 18 (n=99,111)	116.9 mcmol/L Standard Deviation 33.1	114.2 mcmol/L Standard Deviation 30.4
Serum Creatinine (On-Therapy Analysis) Month 24 (n=86,109)	122.9 mcmol/L Standard Deviation 48.8	117.5 mcmol/L Standard Deviation 42.8

SECONDARY outcome

Timeframe: Baseline, Months 6, 12, 18, and 24

Population: On-Therapy Population: all participants who remained on assigned study therapy up to the point of discontinuation. n=number of participants assessed for the specified parameter at a given visit.

Serum creatinine was measured in mcmol/L. Baseline was defined as the last assessment prior to first administration of study drug.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Randomization in Serum Creatinine (On-Therapy Analysis) Month 6 (n=125,120)	-4.1 mcmol/L Standard Error 2.0	-0.0 mcmol/L Standard Error 1.4
Change From Randomization in Serum Creatinine (On-Therapy Analysis) Month 12 (n=109,116)	-0.3 mcmol/L Standard Error 2.9	-7.0 mcmol/L Standard Error 1.9
Change From Randomization in Serum Creatinine (On-Therapy Analysis) Month 18 (n=99,111)	-3.0 mcmol/L Standard Error 2.5	-1.9 mcmol/L Standard Error 2.3
Change From Randomization in Serum Creatinine (On-Therapy Analysis) Month 24 (n=86,109)	3.2 mcmol/L Standard Error 4.6	0.5 mcmol/L Standard Error 3.7

SECONDARY outcome

Timeframe: Post-randomization to Month 24 post-transplantation

Population: ITT Population

Biopsy-confirmed acute rejection was defined according to updated Banff criteria (2007) for renal allograft rejection. Graft loss was defined as physical loss (nephrectomy or retransplantation), functional loss (requiring dialysis for greater than or equal to [≥]56 days with no return of graft function), or death.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation	11.5 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: Post-randomization to Months 12 and 24 Post-Transplantation

Population: ITT Population

Graft loss was defined as physical loss (nephrectomy or retransplantation), functional loss (requiring dialysis for ≥56 days with no return of graft function), or death.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization Month 12	0.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization Month 24	3.8 percentage of participants	0.8 percentage of participants

SECONDARY outcome

Timeframe: Post-Randomization to 6, 12, 18, and 24 months Post-Transplantation

Population: ITT Population

BCAR was defined according to updated Banff criteria (2007) for renal allograft rejection.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation Month 18	6.9 percentage of participants	1.6 percentage of participants
Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation Month 6	1.5 percentage of participants	0.0 percentage of participants
Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation Month 12	5.3 percentage of participants	0.8 percentage of participants
Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation Month 24	8.4 percentage of participants	1.6 percentage of participants

SECONDARY outcome

Timeframe: Months 12 and 24

Population: ITT Population

Defined as the first BCAR occurring during the On-Therapy period based on the ITT population. Time to first BCAR was the days from transplantation to the date of BCAR.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months Month 12	5.1 percentage of participants	0.0 percentage of participants
Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months Month 24	9.3 percentage of participants	0.9 percentage of participants

SECONDARY outcome

Timeframe: Months 6, 12, 18, and 24

Population: ITT Population

BCAR was categorized as antibody-mediated (AM) or T-cell. AM BCAR severity was graded as Grade I (mild), Grade II (moderate), and Grade III (severe). T-cell BCAR severity was graded as 'Grade Ia, Ib (mild), Grade IIa, IIb (moderate), and Grade III (severe). If a participant had both T-cell BCAR and antibody-mediated BCAR on the first rejection, the participant was counted in each category.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 6, AM Grade I	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 6, AM Grade II	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 6, AM Grade III	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 6, T-cell Grade Ia, Ib	2 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 6, T-cell Grade IIa, IIb	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 6, T-cell Grade III	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 12, AM Grade I	1 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 12, AM Grade II	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 12, AM Grade III	1 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 12, T-cell Grade Ia, Ib	5 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 12, T-cell Grade IIa, IIb	1 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 12, T-cell Grade III	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 18, AM Grade I	1 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 18, AM Grade II	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 18, AM Grade III	1 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 18, T-cell Grade Ia, Ib	7 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 18, T-cell Grade IIa, IIb	1 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 18, T-cell Grade III	0 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 24, AM Grade I	2 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 24, AM Grade II	1 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 24, AM Grade III	1 participants	0 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 24, T-cell Grade Ia, Ib	8 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 24, T-cell Grade IIa, IIb	1 participants	1 participants
Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant Month 24, T-cell Grade III	0 participants	0 participants

SECONDARY outcome

Timeframe: On Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation)

Population: Safety Population; only participants with an AE of rejection were included in the analysis.

Number of participants who experienced an adverse event (AE) of rejection was used as the denominator in the determination of percentage of participants with antibody use in treatment of acute rejection.

Outcome measures

Measure	Sirolimus n=15 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=4 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Antibody Use in Treatment of Acute Rejection On-therapy Period	60.0 percentage of participants	75.0 percentage of participants
Percentage of Participants With Antibody Use in Treatment of Acute Rejection Off-therapy Period	40.0 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

Anemia was defined as hemoglobin less than or equal to (≤)10 grams per deciliter (g/dL); leukopenia was defined as white blood cell (WBC) count ≤2000 per cubic millimeters (/mm^3); and thrombocytopenia was defined as platelets ≤100,000/mm^3. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=122 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia Baseline (n=131,122)	4.6 percentage of participants	1.6 percentage of participants
Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia Month 12 (n=110,116)	9.1 percentage of participants	2.6 percentage of participants
Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia Month 24 (n=89,112)	3.4 percentage of participants	4.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

Parameters assessed included total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C); collected when participant was in a fasting state.

Outcome measures

Measure	Sirolimus n=96 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=107 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) TC, Change at Month 12 (n=96,107)	0.66 mmol/L Standard Error 0.10	-0.12 mmol/L Standard Error 0.07
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) TC, Change at Month 24 (n=74,88)	0.51 mmol/L Standard Error 0.14	-0.08 mmol/L Standard Error 0.09
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) HDL-C, Change at Month 12 (n=90,99)	-0.00 mmol/L Standard Error 0.03	0.01 mmol/L Standard Error 0.02
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) HDL-C, Change at Month 24 (n=69,81)	0.01 mmol/L Standard Error 0.04	0.01 mmol/L Standard Error 0.03
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) LDL-C, Change at Month 12 (n=87,98)	0.43 mmol/L Standard Error 0.09	-0.06 mmol/L Standard Error 0.07
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) LDL-C, Change at Month 24 (n=66,78)	0.34 mmol/L Standard Error 0.13	-0.06 mmol/L Standard Error 0.08
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) Triglycerides, Change at Month 12 (n=94,104)	0.47 mmol/L Standard Error 0.11	-0.18 mmol/L Standard Error 0.07
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) Triglycerides, Change at Month 24 (n=73,86)	0.43 mmol/L Standard Error 0.10	0.07 mmol/L Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, Months 12 and 24

Population: ITT Population

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 24, Lipid-lowering agents	47.3 percentage of participants	49.6 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Baseline, Anti-hypertensives	95.4 percentage of participants	92.7 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 12, Anti-hypertensives	75.6 percentage of participants	69.9 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 24, Anti-hypertensives	61.8 percentage of participants	65.9 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Baseline, Diabetes agents (insulin)	46.6 percentage of participants	47.2 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 12, Diabetes agents (insulin)	26.0 percentage of participants	26.0 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 24, Diabetes agents (insulin)	18.3 percentage of participants	25.2 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Baseline, Diabetes agents (non-insulin)	14.5 percentage of participants	17.9 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 12, Diabetes agents (non-insulin)	10.7 percentage of participants	13.8 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 24, Diabetes agents (non-insulin)	9.2 percentage of participants	13.0 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Baseline, Lipid-lowering agents	46.6 percentage of participants	60.2 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 12, Lipid-lowering agents	55.7 percentage of participants	54.5 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Baseline, ESAs	50.4 percentage of participants	43.1 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 12, ESAs	7.6 percentage of participants	2.4 percentage of participants
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) Month 24, ESAs	3.8 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Months 12 and 24

Population: Safety Population; n=number of participants assessed for the specified parameter at a given visit.

Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.

Outcome measures

Measure	Sirolimus n=127 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=120 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr) Baseline (n=127,120)	0.180 UPr/Cr Standard Deviation 0.1413	0.195 UPr/Cr Standard Deviation 0.1477
Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr) Month 12 (n=112,108)	0.353 UPr/Cr Standard Deviation 0.3677	0.208 UPr/Cr Standard Deviation 0.2234
Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr) Month 24 (n=102,106)	0.510 UPr/Cr Standard Deviation 0.7887	0.300 UPr/Cr Standard Deviation 0.6154

SECONDARY outcome

Timeframe: Pre-randomization, On-Therapy Period (up to 21 months post-randomization), and Off-Therapy Period (up to 24 months post-transplantation)

Population: ITT Population

Included ACEI or ARB use prior to randomization, during the on-therapy period (up to 19 to 21 months post randomization) and the off-therapy period (up to 24 months post-transplantation).

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use Pre-randomization	46.6 percentage of participants	46.3 percentage of participants
Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use On-Therapy Period	43.5 percentage of participants	29.3 percentage of participants
Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use Off-Therapy Period	32.1 percentage of participants	18.7 percentage of participants

SECONDARY outcome

Timeframe: From randomization up to 24 months after transplantation (On-Therapy)

Population: Safety Population

Includes adverse events based on categorization by the investigator as stomatitis, regardless of the event preferred term in Medical Dictionary for Regulatory Activities (MedDRA)

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Stomatitis	28.2 percentage of participants	1.6 percentage of participants

SECONDARY outcome

Timeframe: On-Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation)

Population: ITT Population

Included treatments (analgesics, dental paste, topical antifungal, topical steroids, or other) prior to randomization, during the on-therapy period (up to 19 to 21 months post-randomization) and the off-therapy period (up to 24 months post-transplantation).

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type On-Therapy Period, any treatment	17.6 percentage of participants	2.4 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type Off-Therapy Period, any treatment	3.1 percentage of participants	1.6 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type On-Therapy, analgesics	0.8 percentage of participants	0.0 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type On-Therapy, dental paste	3.8 percentage of participants	0.8 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type On-Therapy, topical steroids	5.3 percentage of participants	0.0 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type On-Therapy, other	10.7 percentage of participants	2.4 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type Off-Therapy, topical steroids	1.5 percentage of participants	0.0 percentage of participants
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type Off-Therapy, other	1.5 percentage of participants	1.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

Ratio of hemoglobin A1c to normal hemoglobin.

Outcome measures

Measure	Sirolimus n=86 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=98 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])	-0.00 L/L Standard Error 0.00	0.00 L/L Standard Error 0.00

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

Outcome measures

Measure	Sirolimus n=101 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=112 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)	-0.50 mmol Standard Error 0.31	-0.23 mmol Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

Outcome measures

Measure	Sirolimus n=71 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=84 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])	27.25 pmol/L Standard Error 21.97	17.14 pmol/L Standard Error 11.85

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

Outcome measures

Measure	Sirolimus n=104 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=113 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])	1.61 kg Standard Error 0.51	2.03 kg Standard Error 0.44

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

Outcome measures

Measure	Sirolimus n=98 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=105 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])	1.13 cm Standard Error 0.73	2.21 cm Standard Error 1.00

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

The HOMA-IR measures insulin resistance based on fasting glucose and insulin measurements:

HOMA-IR = fasting plasma glucose (mmol/L) multiplied by (*) fasting plasma insulin in microunits per liter (µU/L) divided by (/) 22.5.

Participants taking insulin within 12 hours were excluded from the analysis.

Outcome measures

Measure	Sirolimus n=66 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=77 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)	1.14 insulin resistance score Standard Error 1.37	1.10 insulin resistance score Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population.

HOMA-B = 20 * insulin (µU/L) / fasting plasma glucose (mmol/L) minus (-) 3.5 Participants taking insulin within 12 hours were excluded from the analysis.

Outcome measures

Measure	Sirolimus n=66 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=77 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)	230.23 percentage beta cell function Standard Error 214.68	26.05 percentage beta cell function Standard Error 21.99

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Safety Population

BMI = Weight (kg)/(Height*Height) (square meters [m^2]).

Outcome measures

Measure	Sirolimus n=101 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=109 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2])	0.53 kg/m^2 Standard Error 0.18	0.75 kg/m^2 Standard Error 0.15

SECONDARY outcome

Timeframe: From Baseline to On-Therapy Month 12, from Baseline to On-Therapy Month 24, and from On-Therapy Month 12 up to On-Therapy Month 24

Population: Safety Population; participants at risk of new-onset diabetes mellitus at the beginning of the analysis interval were included and those with pre-existing diabetes were excluded from the analysis. n=number of participants assessed for the specified parameter at a given visit.

Participants were considered as having new onset diabetes during the On-therapy period if any of the below events emerged from baseline to Month 24: 1) at least 30 days continuous, or at least 25 days non-stop (without gap) use of any diabetic treatment after randomization; 2) a fasting glucose greater than or equal to (≥)126 milligrams per deciliter (mg/dL) after randomization; or 3) a non-fasting glucose ≥200 mg/dL after randomization, were included in the new-onset diabetes population. Events at Months 12 or 24 occurred from baseline to On-therapy Month 12 and from On-therapy Months 12 to 24, respectively.

Outcome measures

Measure	Sirolimus n=82 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=72 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With New-Onset Diabetes New onset (n=82,72)	18.3 percentage of participants	5.6 percentage of participants
Percentage of Participants With New-Onset Diabetes New onset at 1 year (n=82,72)	14.6 percentage of participants	2.8 percentage of participants
Percentage of Participants With New-Onset Diabetes New onset at 2 years (n=70,70)	4.3 percentage of participants	2.9 percentage of participants

SECONDARY outcome

Timeframe: 12 Months and 24 Months

Population: Safety Population. Only participants with new-onset diabetes mellitus at the beginning of the analysis interval were included; those with pre-existing diabetes were excluded from the analysis.

Participants were considered as having new onset diabetes during the On-therapy period if any of the below events emerged between baseline and Month 12 or Month 24: 1) at least 30 days continuous, or at least 25 days non-stop (without gap) use of any diabetic treatment after randomization; 2) a fasting glucose ≥126 mg/dL after randomization; or 3) a non-fasting glucose ≥200 mg/dL after randomization.

Outcome measures

Measure	Sirolimus n=15 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=4 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin) Insulin (12-Month)	13.3 percentage of participants	0.0 percentage of participants
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin) Insulin (24-Month)	6.7 percentage of participants	25.0 percentage of participants
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin) Non-insulin (12-Month)	13.3 percentage of participants	0.0 percentage of participants
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin) Non-Insulin (24-Month)	13.3 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: From randomization up to 24 months after transplantation (On-Therapy)

Population: Safety Population

Includes adverse events based on categorization by the investigator as 'infection', regardless of the event preferred term in MedDRA.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Infection	61.8 percentage of participants	52.0 percentage of participants

SECONDARY outcome

Timeframe: From randomization up to 24 months after transplantation (On-Therapy)

Population: Safety Population

Includes adverse event terms reported by the investigator to be attributed to the organism 'cytomegalovirus', regardless of the preferred term in MedDRA.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Cytomegalovirus (CMV) Infection	3.1 percentage of participants	3.3 percentage of participants

SECONDARY outcome

Timeframe: From randomization up to 24 months after transplantation (On-Therapy)

Population: Safety Population

Includes adverse event terms reported by the investigator to be attributed to the organism 'polyomavirus', regardless of the preferred term in MedDRA.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Polyomavirus Infection	3.8 percentage of participants	7.3 percentage of participants

SECONDARY outcome

Timeframe: From randomization up to 24 months after transplantation (On-Therapy)

Population: Safety Population

Includes any adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferred term in MedDRA.

Outcome measures

Measure	Sirolimus n=131 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 Participants Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Percentage of Participants With Malignancy	3.1 percentage of participants	7.3 percentage of participants

Adverse Events

Sirolimus

Serious events: 50 serious events

Other events: 116 other events

Deaths: 0 deaths

Tacrolimus

Serious events: 38 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sirolimus n=131 participants at risk Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 participants at risk Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Infections and infestations Gastroenteritis viral	1.5% 2/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile neutropenia	1.5% 2/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Pancytopenia	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Polycythaemia	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial infarction	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hyperparathyroidism tertiary	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Flatulence	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gingivitis ulcerative	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Mouth ulceration	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Small intestinal obstruction	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Granuloma	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	1.5% 2/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pseudopolyp	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	3.1% 4/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Sudden cardiac death	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Anaphylactic reaction	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Kidney transplant rejection	2.3% 3/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Transplant rejection	8.4% 11/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Acute sinusitis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Ateriovenous fistula site infection	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacteraemia	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacterial infection	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacterial pyelonephritis	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacterial sepsis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis staphylococcal	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Chronic sinusitis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Cytomegalovirus infection	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Diabetic foot infection	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes zoster	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Infection	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Osteomyelitis	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Osteomyelitis bacterial	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	4.6% 6/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.4% 3/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia bacterial	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia cryptococcal	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Polyomavirus-associated nephropathy	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis acute	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Respriatory tract infection	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Respiratory tract infection viral	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	1.5% 2/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Staphylococcal infection	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	3.8% 5/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urosepsis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Wound infection	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Graft dysfunction	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Periprosthetic fracture	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Immunosuppressant drug level increased	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Transaminases increased	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Flank pain	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.4% 3/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of unknown primary site	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic squamous cell carcinoma	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic uterine cancer	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	3.3% 4/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Convulsion	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Migraine	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Thalamic infarction	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Transient ischaemic attack	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Major depression	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal artery stenosis	2.3% 3/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal cyst ruptured	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure acute	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal impairment	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Tubulointerstitial nephritis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Vesicoureteric reflux	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Ovarian cyst	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Prostatitis	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.76% 1/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	1.5% 2/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertensive crisis	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Sirolimus n=131 participants at risk Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks \[maximum of 4 weeks\] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil \[MMF\] or mycophenolate sodium \[MPS\]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.	Tacrolimus n=123 participants at risk Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Blood and lymphatic system disorders Leukopenia	8.4% 11/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.3% 9/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Polycythaemia	1.5% 2/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.7% 7/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Apthous stomatitis	9.9% 13/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	16.8% 22/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.8% 12/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Mouth ulceration	12.2% 16/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	5.3% 7/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.3% 9/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	8.4% 11/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	3.1% 4/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.7% 7/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	19.1% 25/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.3% 9/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	9.9% 13/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.9% 6/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	5.3% 7/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.9% 6/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	16.8% 22/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.6% 13/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	10.7% 14/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.5% 8/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	6.1% 8/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.1% 5/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Weight increased	5.3% 7/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	3.3% 4/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dyslipidemia	11.5% 15/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.4% 3/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypercholesterolaemia	5.3% 7/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperglycaemia	6.1% 8/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperlipidaemia	10.7% 14/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	3.3% 4/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	6.1% 8/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	4.6% 6/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	7.3% 9/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	12.2% 16/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.7% 7/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Tremor	0.00% 0/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.5% 8/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Proteinuria	14.5% 19/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	1.6% 2/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	6.9% 9/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.9% 6/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 7/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.4% 3/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Acne	14.5% 19/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.81% 1/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	8.4% 11/131 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	8.9% 11/123 • From randomization up to 24 months after transplantation (plus [+]4 weeks) for adverse events (AEs) and serious AEs (SAEs). The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER