Trial Outcomes & Findings for A Study of the Correlation Between Pharmacokinetic and Pharmacodynamic Parameters of CellCept (Mycophenolate Mofetil). (NCT NCT01292226)

Last Updated: 2016-05-12

Results Overview

Diagnosis of acute rejection was suspected in any participant with an increase in serum creatinine greater than or equal to (≥) 25 percent (%). All suspected acute rejections were confirmed by biopsy. The start date of acute rejection was identified as the date of biopsy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

Day 1, Weeks 2, 4, 12, 24, and 28

Results posted on

2016-05-12

Participant Flow

Participant milestones

Participant milestones
Measure	Mycophenolate Mofetil (MMF) Monotherapy Participants received an initial dose of MMF 1 gram (g), orally (PO), twice per day (BID), started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Overall Study STARTED	45
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Mycophenolate Mofetil (MMF) Monotherapy Participants received an initial dose of MMF 1 gram (g), orally (PO), twice per day (BID), started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Overall Study Adverse Event	5
Overall Study Death	1
Overall Study Graft loss	1
Overall Study Protocol Violation	3
Overall Study Withdrawal by Subject	1
Overall Study Other	2

Baseline Characteristics

A Study of the Correlation Between Pharmacokinetic and Pharmacodynamic Parameters of CellCept (Mycophenolate Mofetil).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MMF Monotherapy n=45 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Age, Continuous	46.60 years STANDARD_DEVIATION 9.92 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1, Weeks 2, 4, 12, 24, and 28

Population: Intent-to-treat (ITT) population: all eligible participants who had at least baseline (BL) and 1 assessment of pharmacokinetics (PK) and pharmacodynamics (PD). Acute rejection was analyzed in any participant with an increase in serum creatinine of 25%.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=44 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants With Acute Rejection	9.1 percentage of participants

PRIMARY outcome

Timeframe: Day 1, Weeks 2, 4, 12, 24, and 28

Population: ITT population; only participants with acute or biopsy-proven rejection were included in the analysis.

The mean time, in days, from the date of enrollment to date of biopsy confirming acute rejection.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=6 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Time to Rejection	23.67 days Standard Deviation 21.44

PRIMARY outcome

Timeframe: Day 1, Weeks 2, 4, 12, 24, and 28

Population: ITT population

BPAR was defined according to 1997 Banff Criteria as a biopsy Banff grade of IA, IB, IIA, IIB, or III. Grade IA was defined as significant interstitial infiltration with greater than (\>)25% of parenchyma affected, and foci of moderate tubulitis with \>4 mononuclear cells per tubular cross section or group of 10 tubular cells. Grade IB was defined as significant interstitial infiltration with \>25% parenchyma affected, and foci of severe tubulitis with \>10% mononuclear cells per tubular cross section or group of 10 tubular cells. Grade IIA was defined as mild to moderate intimal arteritis. Grade IIB was defined as severe intimal arteritis comprising \>25% of the luminal area. Grade III was defined as transmural arteritis and/or arterial fibrinoid changes and necrosis of medial smooth muscle cells.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=44 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)	4.5 percentage of participants

SECONDARY outcome

Timeframe: Day 1, Weeks 2, 4, 12, 24, and 28

Population: ITT population

An allograft was presumed to be lost if a participant started dialysis and was not able to subsequently be removed from dialysis.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=44 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants With Graft Loss	2.3 percentage of participants

SECONDARY outcome

Timeframe: Day 1, Weeks 2, 4, 12, 24, and 28

Population: ITT population

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=44 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants Surviving	97.7 percentage of participants

SECONDARY outcome

Timeframe: Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

Drug quantification of total MPA (micrograms per milliliter \[mcg/mL\]) in the plasma was measured at time (T) = 0 minutes (min), 40 mins, and 120 mins.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=491 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, Week 2 (n=41)	1.75 mcg/mL Standard Deviation 1.49
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, Week 4 (n=42)	1.87 mcg/mL Standard Deviation 1.62
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, Week 12 (n=35)	1.79 mcg/mL Standard Deviation 1.04
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, Week 24 (n=35)	1.90 mcg/mL Standard Deviation 1.53
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, safety follow-up (n=3)	1.16 mcg/mL Standard Deviation 0.22
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, unscheduled visit (n=7)	1.32 mcg/mL Standard Deviation 0.67
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=0, overall mean value (n=163)	1.79 mcg/mL Standard Deviation 1.40
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, Week 2 (n=43)	6.44 mcg/mL Standard Deviation 4.37
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, Week 4 (n=42)	6.96 mcg/mL Standard Deviation 3.92
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, Week 12 (n=35)	7.23 mcg/mL Standard Deviation 4.27
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, Week 24 (n=35)	6.47 mcg/mL Standard Deviation 3.35
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, safety follow-up (n=3)	5.71 mcg/mL Standard Deviation 0.55
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, unscheduled visit (n=7)	4.06 mcg/mL Standard Deviation 1.05
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=40, overall mean value (n=165)	6.63 mcg/mL Standard Deviation 3.91
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, Week 2 (n=41)	8.86 mcg/mL Standard Deviation 7.30
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, Week 4 (n=42)	8.95 mcg/mL Standard Deviation 6.33
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, Week 12 (n=35)	8.57 mcg/mL Standard Deviation 6.71
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, safety follow-up (n=3)	4.91 mcg/mL Standard Deviation 2.09
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, Week 24 (n=35)	10.04 mcg/mL Standard Deviation 6.91
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, unscheduled visit (n=7)	7.03 mcg/mL Standard Deviation 5.31
Total Mycophenolate Acid (MPA) by Visit and Timepoint T=120, overall mean value (n=163)	8.92 mcg/mL Standard Deviation 6.68

SECONDARY outcome

Timeframe: Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

Drug quantification of free MPA in the plasma was measured at T = 0, 40, and 120 mins.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=482 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Free MPA (mcg/mL) by Visit T=0, unscheduled visit (n=7)	0.04 mcg/mL Standard Deviation 0.03
Free MPA (mcg/mL) by Visit T=0, overall mean value (n=154)	0.03 mcg/mL Standard Deviation 0.03
Free MPA (mcg/mL) by Visit T=0, Week 2 (n=40)	0.03 mcg/mL Standard Deviation 0.03
Free MPA (mcg/mL) by Visit T=0, Week 4 (n=39)	0.04 mcg/mL Standard Deviation 0.03
Free MPA (mcg/mL) by Visit T=0, Week 12 (n=33)	0.03 mcg/mL Standard Deviation 0.02
Free MPA (mcg/mL) by Visit T=0, Week 24 (n=32)	0.03 mcg/mL Standard Deviation 0.02
Free MPA (mcg/mL) by Visit T=0, safety follow-up (n=3)	0.01 mcg/mL Standard Deviation 0.01
Free MPA (mcg/mL) by Visit T=40, Week 2 (n=41)	0.11 mcg/mL Standard Deviation 0.09
Free MPA (mcg/mL) by Visit T=40, Week 4 (n=42)	0.11 mcg/mL Standard Deviation 0.07
Free MPA (mcg/mL) by Visit T=40, Week 12 (n=35)	0.11 mcg/mL Standard Deviation 0.06
Free MPA (mcg/mL) by Visit T=40, Week 24 (n=35)	0.38 mcg/mL Standard Deviation 1.35
Free MPA (mcg/mL) by Visit T=40, safety follow-up (n=3)	0.06 mcg/mL Standard Deviation 0.02
Free MPA (mcg/mL) by Visit T=40, unscheduled visit (n=7)	0.09 mcg/mL Standard Deviation 0.07
Free MPA (mcg/mL) by Visit T=40, overall mean value (n=163)	0.17 mcg/mL Standard Deviation 0.63
Free MPA (mcg/mL) by Visit T=120, Week 2 (n=43)	0.11 mcg/mL Standard Deviation 0.07
Free MPA (mcg/mL) by Visit T=120, Week 4 (n=42)	0.11 mcg/mL Standard Deviation 0.07
Free MPA (mcg/mL) by Visit T=120, Week 12 (n=35)	0.16 mcg/mL Standard Deviation 0.36
Free MPA (mcg/mL) by Visit T=120, Week 24 (n=35)	0.10 mcg/mL Standard Deviation 0.06
Free MPA (mcg/mL) by Visit T=120, safety follow-up (n=3)	0.10 mcg/mL Standard Deviation 0.03
Free MPA (mcg/mL) by Visit T=120, unscheduled visit (n=7)	0.07 mcg/mL Standard Deviation 0.03
Free MPA (mcg/mL) by Visit T=120, overall mean value (n=165)	0.12 mcg/mL Standard Deviation 0.18

SECONDARY outcome

Timeframe: Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28)

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

The AUC0-12 of MPA was estimated on the validated limited sampling strategy, AUC (milligrams multiplied by height over liter \[mg.h/L\]) = 7.182 + 4.607 multiplied by (\*) concentration at 0 minutes (C0)+ 0.998 \* the concentration at 40 minutes (C0.67) + 2.149 \* the concentration at 120 minutes (C2).

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=44 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit Week 2 (n=41)	38.3 mcg*hr/mL Standard Deviation 17.9
MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit Week 4 (n=42)	39.7 mcg*hr/mL Standard Deviation 17.4
MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit Week 12 (n=35)	39.7 mcg*hr/mL Standard Deviation 16.5
MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit Week 24 (n=35)	39.8 mcg*hr/mL Standard Deviation 17.0
MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit Follow-up (n=3)	29.7 mcg*hr/mL Standard Deviation 3.7

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

IMPDH activity in peripheral blood mononuclear cells (PBMCs) was measured at 2 timepoints per visit, 0 and 120 minutes and presented in enzyme units. The unit of measure of enzyme activity is "U". One U is defined as the amount of the enzyme that produces a certain amount of enzymatic activity that is, the amount that catalyzes the conversion of 1 micro mole of substrate per minute under pre-specified conditions (temperature, pH).

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=364 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, BL (n=44)	5.01 enzyme units Standard Deviation 5.17
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, Week 2 (n=42)	3.96 enzyme units Standard Deviation 3.58
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, Week 4 (n=42)	3.89 enzyme units Standard Deviation 2.36
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, Week 12 (n=35)	6.74 enzyme units Standard Deviation 11.79
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, Week 24 (n=34)	9.58 enzyme units Standard Deviation 10.81
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, safety follow-up (n=0)	0 enzyme units Standard Deviation 0
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, unscheduled visit (n=7)	6.00 enzyme units Standard Deviation 6.12
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=0, mean value (n=204)	5.65 enzyme units Standard Deviation 7.54
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, BL (n=0)	0 enzyme units Standard Deviation 0
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, Week 2 (n=42)	3.06 enzyme units Standard Deviation 3.42
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, Week 4 (n=42)	3.10 enzyme units Standard Deviation 2.66
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, Week 12 (n=35)	3.75 enzyme units Standard Deviation 5.02
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, Week 24 (n=34)	6.39 enzyme units Standard Deviation 6.14
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, safety follow-up (n=0)	0 enzyme units Standard Deviation 0
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, unscheduled visit (n=7)	3.89 enzyme units Standard Deviation 1.82
Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint T=120, mean value (n=160)	3.97 enzyme units Standard Deviation 4.46

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

IMPDH I gene expression was measured by real time polymerase chain reaction (QRT-PCR) based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of messenger ribonucleic acid (mRNA) copies per cell (copies/cell).

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=369 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
IMPDH Expression I by Visit and Timepoint T=0, BL (n=44)	2.32 number of mRNA copies/cell Standard Deviation 3.02
IMPDH Expression I by Visit and Timepoint T=0, Week 2 (n=41)	32.29 number of mRNA copies/cell Standard Deviation 188.29
IMPDH Expression I by Visit and Timepoint T=0, Week 4 (n=42)	3.16 number of mRNA copies/cell Standard Deviation 8.59
IMPDH Expression I by Visit and Timepoint T=0, Week 12 (n=34)	4.10 number of mRNA copies/cell Standard Deviation 15.09
IMPDH Expression I by Visit and Timepoint T=0, Week 24 (n=34)	1.95 number of mRNA copies/cell Standard Deviation 2.94
IMPDH Expression I by Visit and Timepoint T=0, safety follow-up (n=3)	11803.48 number of mRNA copies/cell Standard Deviation 20432.48
IMPDH Expression I by Visit and Timepoint T=0, unscheduled visit (n=7)	4.00 number of mRNA copies/cell Standard Deviation 3.84
IMPDH Expression I by Visit and Timepoint T=0, mean value (n=205)	181.48 number of mRNA copies/cell Standard Deviation 2473.05
IMPDH Expression I by Visit and Timepoint T=120, BL (n=0)	0 number of mRNA copies/cell Standard Deviation 0
IMPDH Expression I by Visit and Timepoint T=120, Week 2 (n=43)	4146.17 number of mRNA copies/cell Standard Deviation 14891.57
IMPDH Expression I by Visit and Timepoint T=120, Week 4 (n=42)	1692.11 number of mRNA copies/cell Standard Deviation 6690.21
IMPDH Expression I by Visit and Timepoint T=120, Week 12 (n=35)	1556.06 number of mRNA copies/cell Standard Deviation 5856.17
IMPDH Expression I by Visit and Timepoint T=120, Week 24 (n=34)	3.02 number of mRNA copies/cell Standard Deviation 7.53
IMPDH Expression I by Visit and Timepoint T=120, safety follow-up (n=3)	107.30 number of mRNA copies/cell Standard Deviation 179.38
IMPDH Expression I by Visit and Timepoint T=120, unscheduled visit (n=7)	1038.52 number of mRNA copies/cell Standard Deviation 1781.89
IMPDH Expression I by Visit and Timepoint T=120, mean value (n=164)	1899.45 number of mRNA copies/cell Standard Deviation 8824.89

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

IMPDH II gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=369 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
IMPDH Expression II by Visit and Timepoint T=0, BL (n=44)	115.33 number of mRNA copies/cell Standard Deviation 19.81
IMPDH Expression II by Visit and Timepoint T=0, Week 2 (n=41)	113.43 number of mRNA copies/cell Standard Deviation 21.67
IMPDH Expression II by Visit and Timepoint T=0, Week 4 (n=42)	117.16 number of mRNA copies/cell Standard Deviation 30.72
IMPDH Expression II by Visit and Timepoint T=0, Week 12 (n=34)	112.43 number of mRNA copies/cell Standard Deviation 24.57
IMPDH Expression II by Visit and Timepoint T=0, Week 24 (n=34)	114.21 number of mRNA copies/cell Standard Deviation 19.79
IMPDH Expression II by Visit and Timepoint T=0, safety follow-up (n=3)	123.86 number of mRNA copies/cell Standard Deviation 37.61
IMPDH Expression II by Visit and Timepoint T=0, unscheduled visit (n=7)	116.57 number of mRNA copies/cell Standard Deviation 19.25
IMPDH Expression II by Visit and Timepoint T=0, mean value (n=205)	114.82 number of mRNA copies/cell Standard Deviation 23.54
IMPDH Expression II by Visit and Timepoint T=120, BL (n=0)	0 number of mRNA copies/cell Standard Deviation 0
IMPDH Expression II by Visit and Timepoint T=120, Week 2 (n=43)	304.64 number of mRNA copies/cell Standard Deviation 309.26
IMPDH Expression II by Visit and Timepoint T=120, Week 4 (n=42)	148.32 number of mRNA copies/cell Standard Deviation 206.39
IMPDH Expression II by Visit and Timepoint T=120, Week 12 (n=35)	143.11 number of mRNA copies/cell Standard Deviation 82.95
IMPDH Expression II by Visit and Timepoint T=120, Week 24 (n=34)	109.00 number of mRNA copies/cell Standard Deviation 22.81
IMPDH Expression II by Visit and Timepoint T=120, safety follow-up (n=3)	140.51 number of mRNA copies/cell Standard Deviation 42.37
IMPDH Expression II by Visit and Timepoint T=120, unscheduled visit (n=7)	167.19 number of mRNA copies/cell Standard Deviation 155.73
IMPDH Expression II by Visit and Timepoint T=120, mean value (n=164)	180.71 number of mRNA copies/cell Standard Deviation 208.68

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

IL-8 gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=369 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, BL (n=44)	4532.72 number of mRNA copies/cell Standard Deviation 11598.93
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, Week 2 (n=41)	29960.41 number of mRNA copies/cell Standard Deviation 128979.24
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, Week 4 (n=42)	54101.30 number of mRNA copies/cell Standard Deviation 262581.32
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, Week 12 (n=34)	1829.87 number of mRNA copies/cell Standard Deviation 6411.17
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, Week 24 (n=34)	10391.60 number of mRNA copies/cell Standard Deviation 42574.52
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, safety follow-up (n=3)	1254.29 number of mRNA copies/cell Standard Deviation 1150.40
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, unscheduled visit (n=7)	19148.94 number of mRNA copies/cell Standard Deviation 49991.25
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=0, mean value (n=205)	20748.32 number of mRNA copies/cell Standard Deviation 1333817.10
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, BL (n=0)	0.0 number of mRNA copies/cell Standard Deviation 0.0
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, Week 2 (n=43)	1028.93 number of mRNA copies/cell Standard Deviation 4210.43
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, Week 4 (n=42)	21227.11 number of mRNA copies/cell Standard Deviation 103517.73
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, Week 12 (n=35)	12022.83 number of mRNA copies/cell Standard Deviation 63647.48
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, Week 24 (n=34)	9418.65 number of mRNA copies/cell Standard Deviation 29084.00
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, safety follow-up (n=3)	397887.30 number of mRNA copies/cell Standard Deviation 688477.81
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, unscheduled visit (n=7)	220.14 number of mRNA copies/cell Standard Deviation 457.26
Interleukin 8 (IL-8) Expression by Visit and Timepoint T=120, mean value (n=164)	17512.31 number of mRNA copies/cell Standard Deviation 110920.39

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits

Population: ITT population; n=number of samples analyzed.

TNF gene expression was measured by QRT-PCR based cytokine measurement of PBMCs at 2 timepoints per visit, 0 and 120 minutes and expressed as number of mRNA copies/cell.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=369 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, unscheduled visit (n=7)	19148.94 number of mRNA copies/cell Standard Deviation 49991.25
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, BL (n=0)	0 number of mRNA copies/cell Standard Deviation 0
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, BL (n=44)	4532.72 number of mRNA copies/cell Standard Deviation 11598.93
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, Week 2 (n=41)	29960.41 number of mRNA copies/cell Standard Deviation 128979.24
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, Week 4 (n=42)	54101.30 number of mRNA copies/cell Standard Deviation 262581.32
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, Week 12 (n=34)	1829.87 number of mRNA copies/cell Standard Deviation 6411.17
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, Week 24 (n=34)	10391.60 number of mRNA copies/cell Standard Deviation 42574.52
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, safety follow-up (n=3)	1254.29 number of mRNA copies/cell Standard Deviation 1150.40
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=0, mean value (n=205)	20748.32 number of mRNA copies/cell Standard Deviation 133817.10
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, Week 2 (n=43)	1028.93 number of mRNA copies/cell Standard Deviation 4210.43
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, Week 4 (n=42)	21227.11 number of mRNA copies/cell Standard Deviation 103517.73
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, Week 12 (n=35)	12022.83 number of mRNA copies/cell Standard Deviation 63647.48
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, Week 24 (n=34)	9418.65 number of mRNA copies/cell Standard Deviation 29084.00
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, safety follow-up (n=3)	397887.30 number of mRNA copies/cell Standard Deviation 688477.81
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, unscheduled visit (n=7)	220.14 number of mRNA copies/cell Standard Deviation 457.26
Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint T=120, mean value (n=164)	17512.31 number of mRNA copies/cell Standard Deviation 110920.39

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)

Population: Safety population: all enrolled participants

Infections were graded according to the World Health Organization (WHO) worst grade observed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=45 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants With Infection Acarodermatitis (mild)	2.22 percentage of participants
Percentage of Participants With Infection Bronchitis (moderate)	2.22 percentage of participants
Percentage of Participants With Infection Cytomegalovirus (CMV) infection (mild)	13.33 percentage of participants
Percentage of Participants With Infection CMV infection (moderate)	8.89 percentage of participants
Percentage of Participants With Infection CMV infection (severe)	4.44 percentage of participants
Percentage of Participants With Infection CMV viraemia (mild)	2.22 percentage of participants
Percentage of Participants With Infection Gastroenteritis proteus (severe)	2.22 percentage of participants
Percentage of Participants With Infection Gastrointestinal infection (severe)	2.22 percentage of participants
Percentage of Participants With Infection Legionella infection (life-threatening)	2.22 percentage of participants
Percentage of Participants With Infection Oral herpes (mild)	2.22 percentage of participants
Percentage of Participants With Infection Sepsis (life-threatening)	2.22 percentage of participants
Percentage of Participants With Infection Tracheitis (mild)	2.22 percentage of participants
Percentage of Participants With Infection Urethritis (mild)	2.22 percentage of participants
Percentage of Participants With Infection Urinary tract infection (mild)	28.89 percentage of participants
Percentage of Participants With Infection Urinary tract infection (moderate)	2.22 percentage of participants

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit)

Population: Safety population

Gastrointestinal adverse events (AEs) according to WHO worst grade observed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=45 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants With Gastrointestinal Toxicities Abdominal pain (moderate)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Abdominal pain (severe)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Anal fissure (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Diarrhoea (mild)	4.44 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Diarrhoea (moderate)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Diarrhoea (severe)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Dyspepsia (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Gastritis (moderate)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Gastritis erosive (moderate)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Gingival hyperplasia (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Haemorrhoids (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Intra-abdominal haematoma (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Nausea (moderate)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Stomatitis (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Vomiting (mild)	2.22 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Vomiting (moderate)	4.44 percentage of participants
Percentage of Participants With Gastrointestinal Toxicities Vomiting (severe)	4.44 percentage of participants

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)

Population: Safety population

Hematological toxicities graded according to WHO worst grade observed (Grade 1=mild, Grade 2=moderate).

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=45 Participants Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Percentage of Participants With Hematologic Toxicity Grade 1 hemoglobin decreased	13.33 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 leukocytes decreased	11.11 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 leukocytes decreased	8.89 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 granulocytes decreased	6.67 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 granulocytes decreased	6.67 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 platelets decreased	6.67 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 bilirubin increased	4.44 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 bilirubin increased	2.22 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 hypoglycemia	4.44 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 alkaline phosphatase increased	13.33 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 alkaline phosphatase increased	2.22 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 aspartate aminotransferase increased	6.67 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 alanine aminotransferase increased	8.89 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 alanine aminotransferase increased	2.22 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 cholesterol increased	26.67 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 cholesterol increased	8.89 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 triglycerides increased	24.44 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 triglycerides increased	2.22 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 1 blood urea nitrogen increased	2.22 percentage of participants
Percentage of Participants With Hematologic Toxicity Grade 2 blood urea nitrogen increased	2.22 percentage of participants

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed.

The Spearman's rank correlation coefficient was computed by ranking the data from 2 time points, 0 minutes and 120 minutes, and using the ranks in the Pearson product-moment correlation formula. In case of ties, the averaged ranks were used.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=305 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity Free MPA, T=0 (n=144)	0.063 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity Free MPA, T=120 (n=153)	0.028 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity Total MPA, T=0 (n=152)	0.034 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity Total MPA, T=120 (n=153)	-0.050 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=290 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels Free MPA, T=0 (n=141)	0.073 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels Free MPA, T=120 (n=143)	-0.024 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels Total MPA, T=0 (n=147)	0.037 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels Total MPA, T=120 (n=143)	-0.140 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=283 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction p Free fraction, T=0 (n=140)	0.047 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction p Free fraction, T=120 (n=143)	0.080 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=305 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels Free MPA, T=0 (n=145)	0.007 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels Free MPA, T=120 (n=153)	0.073 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels Total MPA, T=0 (n=152)	-0.001 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels Total MPA, T=120 (n=153)	0.084 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=297 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction p Free fraction, T=0 (n=144)	-0.027 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction p Free fraction, T=120 (n=153)	0.015 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=353 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection IMPDH I expression, T=0 (n=189)	0.030 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection IMPDH I expression T=120 (n=145)	0.083 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection IMPDH II expression, T=0 (n=196)	-0.062 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection IMPDH II expression (T=120, n=155)	-0.010 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection MPDH Activity, T=0 (n=198)	-0.121 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection IMPDH Activity, T=120 (n=155)	-0.004 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples analyzed.

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=351 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection IMPDH I expression (n=334)	0.045 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection IMPDH II expression (n=351)	0.047 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=351 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity IMPDH I expression (n=334)	-0.116 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity IMPDH II expression (n=351)	-0.004 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=351 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity IMPDH I expression (n=334)	0.082 correlation coefficient
Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity IMPDH II expression (n=351)	0.030 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=308 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection Free MPA (n=300)	-0.020 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection Total MPA (n=308)	0.063 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection AUC MPA (n=152)	0.030 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=308 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity Free MPA (n=300)	-0.004 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity Total MPA (n=308)	-0.037 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity AUC MPA (n=152)	-0.038 correlation coefficient

SECONDARY outcome

Timeframe: BL and Weeks 2, 4, 12, and 24

Population: ITT population; n=number of samples

Outcome measures

Outcome measures
Measure	MMF Monotherapy n=308 Samples Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity Free MPA (n=300)	0.106 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity Total MPA (n=308)	0.142 correlation coefficient
Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity AUC MPA (n=152)	0.187 correlation coefficient

Adverse Events

MMF Monotherapy

Serious events: 20 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MMF Monotherapy n=45 participants at risk Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Renal and urinary disorders Acute tubular necrosis	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Vomiting	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Hydronephrosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Acute renal failure	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations CMV infection	6.7% 3/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Infection due to Legionella and Pseudomonas	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Sepsis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Tubulitis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Ureteral stenosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Proteus mirabilis infection	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Leucopenia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Urinary anastomotic leak	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenocarcinoma	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Gastrointestinal infection	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Acute rejection	6.7% 3/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoma of the bladder	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Acute vascular and interstitial rejection	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Lymphocele	33.3% 15/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Edema of the left leg	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Investigations Increase in creatinine	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.

Other adverse events

Other adverse events
Measure	MMF Monotherapy n=45 participants at risk Participants received an initial dose of MMF 1 g, PO, BID, started within 5 days of transplant, for up to 24 weeks. MMF dose could be titrated to a maximum daily dose of 2 g (minimum daily dose was 1 g). Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.
Infections and infestations Urinary tract infection	48.9% 22/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Cytomegalovirus infection	20.0% 9/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Investigations Blood creatinine increased	17.8% 8/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Investigations Blood cholesterol increased	6.7% 3/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Investigations White blood cell count decreased	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Investigations Alanine aminotransferase increased	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Investigations Blood bilirubin increased	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Vomiting	11.1% 5/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Diarrhoea	15.6% 7/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Abdominal pain	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Gastritis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Gastritis erosive	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Gingival hyperplasia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Haemorrhoids	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Dyspepsia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Nausea	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Stomatitis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	17.8% 8/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hyperuricaemia	15.6% 7/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hypercholesterolemia	8.9% 4/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hyperlipemia	6.7% 3/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hypocalcaemia	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Diabetes mellitus	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Iron deficiency	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Nervous system disorders Headache	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Nervous system disorders Paraesthesia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Pyrexia	26.7% 12/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Oedema peripheral	8.9% 4/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Asthenia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Catheter related infection	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Hearing impaired	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Leukopenia	28.9% 13/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Anaemia	22.2% 10/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Lymphocele	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Antithrombin III deficiency	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Thrombocytopenia	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Bronchitis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Iron deficiency anaemia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Lymphocytopenia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Vascular disorders Hypertension	13.3% 6/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Psychiatric disorders Insomnia	11.1% 5/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Psychiatric disorders Anxiety	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Cardiac disorders Angina pectoris	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Hepatobiliary disorders Cholestasis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Cardiac disorders Erythema	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Cardiac disorders Tachycardia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Renal colic	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Dysuria	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Haematuria	4.4% 2/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Acarodermatitis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Acidosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Hepatobiliary disorders Lipidosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Myopathy	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Nocturia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Tracheitis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Urethritis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Surgical and medical procedures Wound haemorrhage	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Anal fissure	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Vascular disorders Arteriovenous fistula	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Vascular disorders Arteriovenous fistula thrombosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Ear pain	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Blood and lymphatic system disorders Coagulopathy	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Infections and infestations Cytomegalovirus viraemia	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Glomerulosclerosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Surgical and medical procedures Operative haemorrhage	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Post-procedural haemorrhage	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Intra-abdominal haematoma	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Oral herpes	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
General disorders Pharyngolaryngeal pain	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Renal artery stenosis	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
Renal and urinary disorders Perirenal haematoma	2.2% 1/45 • Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks. The safety assessment population included all eligible participants who received at least 1 dose of study treatment.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER