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

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ClinicalTrials.gov Identifier: NCT01292226
Recruitment Status : Completed
First Posted : February 9, 2011
Results First Posted : March 2, 2015
Last Update Posted : May 12, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Kidney Transplantation
Interventions Drug: mycophenolate mofetil
Drug: antibody induction
Drug: Cyclosporine
Drug: corticosteroid
Enrollment 45
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Mycophenolate Mofetil (MMF) Monotherapy
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 45
Completed 32
Not Completed 13
Reason Not Completed
Adverse Event             5
Death             1
Graft loss             1
Protocol Violation             3
Withdrawal by Subject             1
Other             2
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 45
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants
46.60  (9.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
Female
20
  44.4%
Male
25
  55.6%
1.Primary Outcome
Title Percentage of Participants With Acute Rejection
Hide Description 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.
Time Frame Day 1, Weeks 2, 4, 12, 24, and 28
Hide Outcome Measure Data
Hide Analysis Population Description
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%.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Measure Type: Number
Unit of Measure: percentage of participants
9.1
2.Primary Outcome
Title Time to Rejection
Hide Description The mean time, in days, from the date of enrollment to date of biopsy confirming acute rejection.
Time Frame Day 1, Weeks 2, 4, 12, 24, and 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; only participants with acute or biopsy-proven rejection were included in the analysis.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: days
23.67  (21.44)
3.Primary Outcome
Title Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)
Hide Description 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.
Time Frame Day 1, Weeks 2, 4, 12, 24, and 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Measure Type: Number
Unit of Measure: percentage of participants
4.5
4.Secondary Outcome
Title Percentage of Participants With Graft Loss
Hide Description An allograft was presumed to be lost if a participant started dialysis and was not able to subsequently be removed from dialysis.
Time Frame Day 1, Weeks 2, 4, 12, 24, and 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Measure Type: Number
Unit of Measure: percentage of participants
2.3
5.Secondary Outcome
Title Percentage of Participants Surviving
Hide Description [Not Specified]
Time Frame Day 1, Weeks 2, 4, 12, 24, and 28
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Measure Type: Number
Unit of Measure: percentage of participants
97.7
6.Secondary Outcome
Title Total Mycophenolate Acid (MPA) by Visit and Timepoint
Hide Description 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.
Time Frame Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up Visit), and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 491
Mean (Standard Deviation)
Unit of Measure: mcg/mL
T=0, Week 2 (n=41) 1.75  (1.49)
T=0, Week 4 (n=42) 1.87  (1.62)
T=0, Week 12 (n=35) 1.79  (1.04)
T=0, Week 24 (n=35) 1.90  (1.53)
T=0, safety follow-up (n=3) 1.16  (0.22)
T=0, unscheduled visit (n=7) 1.32  (0.67)
T=0, overall mean value (n=163) 1.79  (1.40)
T=40, Week 2 (n=43) 6.44  (4.37)
T=40, Week 4 (n=42) 6.96  (3.92)
T=40, Week 12 (n=35) 7.23  (4.27)
T=40, Week 24 (n=35) 6.47  (3.35)
T=40, safety follow-up (n=3) 5.71  (0.55)
T=40, unscheduled visit (n=7) 4.06  (1.05)
T=40, overall mean value (n=165) 6.63  (3.91)
T=120, Week 2 (n=41) 8.86  (7.30)
T=120, Week 4 (n=42) 8.95  (6.33)
T=120, Week 12 (n=35) 8.57  (6.71)
T=120, safety follow-up (n=3) 4.91  (2.09)
T=120, Week 24 (n=35) 10.04  (6.91)
T=120, unscheduled visit (n=7) 7.03  (5.31)
T=120, overall mean value (n=163) 8.92  (6.68)
7.Secondary Outcome
Title Free MPA (mcg/mL) by Visit
Hide Description Drug quantification of free MPA in the plasma was measured at T = 0, 40, and 120 mins.
Time Frame Weeks 2, 4, 12, 24, safety follow-up (Week 28), and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 482
Mean (Standard Deviation)
Unit of Measure: mcg/mL
T=0, Week 2 (n=40) 0.03  (0.03)
T=0, Week 4 (n=39) 0.04  (0.03)
T=0, Week 12 (n=33) 0.03  (0.02)
T=0, Week 24 (n=32) 0.03  (0.02)
T=0, safety follow-up (n=3) 0.01  (0.01)
T=0, unscheduled visit (n=7) 0.04  (0.03)
T=0, overall mean value (n=154) 0.03  (0.03)
T=40, Week 2 (n=41) 0.11  (0.09)
T=40, Week 4 (n=42) 0.11  (0.07)
T=40, Week 12 (n=35) 0.11  (0.06)
T=40, Week 24 (n=35) 0.38  (1.35)
T=40, safety follow-up (n=3) 0.06  (0.02)
T=40, unscheduled visit (n=7) 0.09  (0.07)
T=40, overall mean value (n=163) 0.17  (0.63)
T=120, Week 2 (n=43) 0.11  (0.07)
T=120, Week 4 (n=42) 0.11  (0.07)
T=120, Week 12 (n=35) 0.16  (0.36)
T=120, Week 24 (n=35) 0.10  (0.06)
T=120, safety follow-up (n=3) 0.10  (0.03)
T=120, unscheduled visit (n=7) 0.07  (0.03)
T=120, overall mean value (n=165) 0.12  (0.18)
8.Secondary Outcome
Title MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by Visit
Hide Description 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).
Time Frame Predose and 40 minutes and 2 hours postdose at Weeks 2, 4, 12, and 24, and at the Safety follow-up (Week 28)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of participants assessed for the specified parameter at a given visit.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: mcg*hr/mL
Week 2 (n=41) 38.3  (17.9)
Week 4 (n=42) 39.7  (17.4)
Week 12 (n=35) 39.7  (16.5)
Week 24 (n=35) 39.8  (17.0)
Follow-up (n=3) 29.7  (3.7)
9.Secondary Outcome
Title Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint
Hide Description 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).
Time Frame BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 364
Mean (Standard Deviation)
Unit of Measure: enzyme units
T=0, BL (n=44) 5.01  (5.17)
T=0, Week 2 (n=42) 3.96  (3.58)
T=0, Week 4 (n=42) 3.89  (2.36)
T=0, Week 12 (n=35) 6.74  (11.79)
T=0, Week 24 (n=34) 9.58  (10.81)
T=0, safety follow-up (n=0) 0  (0)
T=0, unscheduled visit (n=7) 6.00  (6.12)
T=0, mean value (n=204) 5.65  (7.54)
T=120, BL (n=0) 0  (0)
T=120, Week 2 (n=42) 3.06  (3.42)
T=120, Week 4 (n=42) 3.10  (2.66)
T=120, Week 12 (n=35) 3.75  (5.02)
T=120, Week 24 (n=34) 6.39  (6.14)
T=120, safety follow-up (n=0) 0  (0)
T=120, unscheduled visit (n=7) 3.89  (1.82)
T=120, mean value (n=160) 3.97  (4.46)
10.Secondary Outcome
Title IMPDH Expression I by Visit and Timepoint
Hide Description 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).
Time Frame BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 369
Mean (Standard Deviation)
Unit of Measure: number of mRNA copies/cell
T=0, BL (n=44) 2.32  (3.02)
T=0, Week 2 (n=41) 32.29  (188.29)
T=0, Week 4 (n=42) 3.16  (8.59)
T=0, Week 12 (n=34) 4.10  (15.09)
T=0, Week 24 (n=34) 1.95  (2.94)
T=0, safety follow-up (n=3) 11803.48  (20432.48)
T=0, unscheduled visit (n=7) 4.00  (3.84)
T=0, mean value (n=205) 181.48  (2473.05)
T=120, BL (n=0) 0  (0)
T=120, Week 2 (n=43) 4146.17  (14891.57)
T=120, Week 4 (n=42) 1692.11  (6690.21)
T=120, Week 12 (n=35) 1556.06  (5856.17)
T=120, Week 24 (n=34) 3.02  (7.53)
T=120, safety follow-up (n=3) 107.30  (179.38)
T=120, unscheduled visit (n=7) 1038.52  (1781.89)
T=120, mean value (n=164) 1899.45  (8824.89)
11.Secondary Outcome
Title IMPDH Expression II by Visit and Timepoint
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 369
Mean (Standard Deviation)
Unit of Measure: number of mRNA copies/cell
T=0, BL (n=44) 115.33  (19.81)
T=0, Week 2 (n=41) 113.43  (21.67)
T=0, Week 4 (n=42) 117.16  (30.72)
T=0, Week 12 (n=34) 112.43  (24.57)
T=0, Week 24 (n=34) 114.21  (19.79)
T=0, safety follow-up (n=3) 123.86  (37.61)
T=0, unscheduled visit (n=7) 116.57  (19.25)
T=0, mean value (n=205) 114.82  (23.54)
T=120, BL (n=0) 0  (0)
T=120, Week 2 (n=43) 304.64  (309.26)
T=120, Week 4 (n=42) 148.32  (206.39)
T=120, Week 12 (n=35) 143.11  (82.95)
T=120, Week 24 (n=34) 109.00  (22.81)
T=120, safety follow-up (n=3) 140.51  (42.37)
T=120, unscheduled visit (n=7) 167.19  (155.73)
T=120, mean value (n=164) 180.71  (208.68)
12.Secondary Outcome
Title Interleukin 8 (IL-8) Expression by Visit and Timepoint
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 369
Mean (Standard Deviation)
Unit of Measure: number of mRNA copies/cell
T=0, BL (n=44) 4532.72  (11598.93)
T=0, Week 2 (n=41) 29960.41  (128979.24)
T=0, Week 4 (n=42) 54101.30  (262581.32)
T=0, Week 12 (n=34) 1829.87  (6411.17)
T=0, Week 24 (n=34) 10391.60  (42574.52)
T=0, safety follow-up (n=3) 1254.29  (1150.40)
T=0, unscheduled visit (n=7) 19148.94  (49991.25)
T=0, mean value (n=205) 20748.32  (1333817.10)
T=120, BL (n=0) 0.0  (0.0)
T=120, Week 2 (n=43) 1028.93  (4210.43)
T=120, Week 4 (n=42) 21227.11  (103517.73)
T=120, Week 12 (n=35) 12022.83  (63647.48)
T=120, Week 24 (n=34) 9418.65  (29084.00)
T=120, safety follow-up (n=3) 397887.30  (688477.81)
T=120, unscheduled visit (n=7) 220.14  (457.26)
T=120, mean value (n=164) 17512.31  (110920.39)
13.Secondary Outcome
Title Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24, and safety follow-up (Week 28) and any unscheduled visits
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 369
Mean (Standard Deviation)
Unit of Measure: number of mRNA copies/cell
T=0, BL (n=44) 4532.72  (11598.93)
T=0, Week 2 (n=41) 29960.41  (128979.24)
T=0, Week 4 (n=42) 54101.30  (262581.32)
T=0, Week 12 (n=34) 1829.87  (6411.17)
T=0, Week 24 (n=34) 10391.60  (42574.52)
T=0, safety follow-up (n=3) 1254.29  (1150.40)
T=0, unscheduled visit (n=7) 19148.94  (49991.25)
T=0, mean value (n=205) 20748.32  (133817.10)
T=120, BL (n=0) 0  (0)
T=120, Week 2 (n=43) 1028.93  (4210.43)
T=120, Week 4 (n=42) 21227.11  (103517.73)
T=120, Week 12 (n=35) 12022.83  (63647.48)
T=120, Week 24 (n=34) 9418.65  (29084.00)
T=120, safety follow-up (n=3) 397887.30  (688477.81)
T=120, unscheduled visit (n=7) 220.14  (457.26)
T=120, mean value (n=164) 17512.31  (110920.39)
14.Secondary Outcome
Title Percentage of Participants With Infection
Hide Description Infections were graded according to the World Health Organization (WHO) worst grade observed.
Time Frame BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all enrolled participants
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
Acarodermatitis (mild) 2.22
Bronchitis (moderate) 2.22
Cytomegalovirus (CMV) infection (mild) 13.33
CMV infection (moderate) 8.89
CMV infection (severe) 4.44
CMV viraemia (mild) 2.22
Gastroenteritis proteus (severe) 2.22
Gastrointestinal infection (severe) 2.22
Legionella infection (life-threatening) 2.22
Oral herpes (mild) 2.22
Sepsis (life-threatening) 2.22
Tracheitis (mild) 2.22
Urethritis (mild) 2.22
Urinary tract infection (mild) 28.89
Urinary tract infection (moderate) 2.22
15.Secondary Outcome
Title Percentage of Participants With Gastrointestinal Toxicities
Hide Description Gastrointestinal adverse events (AEs) according to WHO worst grade observed.
Time Frame BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-up Visit)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
Abdominal pain (moderate) 2.22
Abdominal pain (severe) 2.22
Anal fissure (mild) 2.22
Diarrhoea (mild) 4.44
Diarrhoea (moderate) 2.22
Diarrhoea (severe) 2.22
Dyspepsia (mild) 2.22
Gastritis (moderate) 2.22
Gastritis erosive (moderate) 2.22
Gingival hyperplasia (mild) 2.22
Haemorrhoids (mild) 2.22
Intra-abdominal haematoma (mild) 2.22
Nausea (moderate) 2.22
Stomatitis (mild) 2.22
Vomiting (mild) 2.22
Vomiting (moderate) 4.44
Vomiting (severe) 4.44
16.Secondary Outcome
Title Percentage of Participants With Hematologic Toxicity
Hide Description Hematological toxicities graded according to WHO worst grade observed (Grade 1=mild, Grade 2=moderate).
Time Frame BL and Weeks 2, 4, 12, 24, and 28 (Safety Follow-Up)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
Grade 1 hemoglobin decreased 13.33
Grade 1 leukocytes decreased 11.11
Grade 2 leukocytes decreased 8.89
Grade 1 granulocytes decreased 6.67
Grade 2 granulocytes decreased 6.67
Grade 1 platelets decreased 6.67
Grade 1 bilirubin increased 4.44
Grade 2 bilirubin increased 2.22
Grade 1 hypoglycemia 4.44
Grade 1 alkaline phosphatase increased 13.33
Grade 2 alkaline phosphatase increased 2.22
Grade 1 aspartate aminotransferase increased 6.67
Grade 1 alanine aminotransferase increased 8.89
Grade 2 alanine aminotransferase increased 2.22
Grade 1 cholesterol increased 26.67
Grade 2 cholesterol increased 8.89
Grade 1 triglycerides increased 24.44
Grade 2 triglycerides increased 2.22
Grade 1 blood urea nitrogen increased 2.22
Grade 2 blood urea nitrogen increased 2.22
17.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 305
Measure Type: Number
Unit of Measure: correlation coefficient
Free MPA, T=0 (n=144) 0.063
Free MPA, T=120 (n=153) 0.028
Total MPA, T=0 (n=152) 0.034
Total MPA, T=120 (n=153) -0.050
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4505
Comments Free MPA, time 0 [trough]
Method ANOVA
Comments Analysis of variance (ANOVA)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7322
Comments Free MPA, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6798
Comments Total MPA, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5410
Comments Total MPA, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
18.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 290
Measure Type: Number
Unit of Measure: correlation coefficient
Free MPA, T=0 (n=141) 0.073
Free MPA, T=120 (n=143) -0.024
Total MPA, T=0 (n=147) 0.037
Total MPA, T=120 (n=143) -0.140
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3892
Comments Free MPA, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6564
Comments Total MPA, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7772
Comments Free MPA, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0958
Comments Total MPA, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
19.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 283
Measure Type: Number
Unit of Measure: correlation coefficient
p Free fraction, T=0 (n=140) 0.047
p Free fraction, T=120 (n=143) 0.080
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5796
Comments Time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3428
Comments Time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
20.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 305
Measure Type: Number
Unit of Measure: correlation coefficient
Free MPA, T=0 (n=145) 0.007
Free MPA, T=120 (n=153) 0.073
Total MPA, T=0 (n=152) -0.001
Total MPA, T=120 (n=153) 0.084
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9372
Comments Free MPA, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9904
Comments Total MPA, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3658
Comments Free MPA, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2987
Comments Total MPA, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
21.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 297
Measure Type: Number
Unit of Measure: correlation coefficient
p Free fraction, T=0 (n=144) -0.027
p Free fraction, T=120 (n=153) 0.015
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7455
Comments time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8504
Comments Time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
22.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 353
Measure Type: Number
Unit of Measure: correlation coefficient
IMPDH I expression, T=0 (n=189) 0.030
IMPDH I expression T=120 (n=145) 0.083
IMPDH II expression, T=0 (n=196) -0.062
IMPDH II expression (T=120, n=155) -0.010
MPDH Activity, T=0 (n=198) -0.121
IMPDH Activity, T=120 (n=155) -0.004
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6847
Comments IMPDH I, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3184
Comments IMPDH I, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3862
Comments IMPDH II, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9040
Comments IMPDH II, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0907
Comments IMPDH activity, time 0 [trough]
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9630
Comments IMPDH activity, time 120 [2 hours after administration at Week 12]
Method ANOVA
Comments [Not Specified]
23.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples analyzed.
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 351
Measure Type: Number
Unit of Measure: correlation coefficient
IMPDH I expression (n=334) 0.045
IMPDH II expression (n=351) 0.047
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4130
Comments IMPDH I
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3823
Comments IMPDH II
Method ANOVA
Comments [Not Specified]
24.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 351
Measure Type: Number
Unit of Measure: correlation coefficient
IMPDH I expression (n=334) -0.116
IMPDH II expression (n=351) -0.004
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0316
Comments IMPDH I
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9440
Comments IMPDH II
Method ANOVA
Comments [Not Specified]
25.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 351
Measure Type: Number
Unit of Measure: correlation coefficient
IMPDH I expression (n=334) 0.082
IMPDH II expression (n=351) 0.030
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1328
Comments IMPDH I
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5760
Comments IMPDH II
Method ANOVA
Comments [Not Specified]
26.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 308
Measure Type: Number
Unit of Measure: correlation coefficient
Free MPA (n=300) -0.020
Total MPA (n=308) 0.063
AUC MPA (n=152) 0.030
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7332
Comments Free MPA
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2681
Comments Total MPA
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7087
Comments AUC MPA
Method ANOVA
Comments [Not Specified]
27.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 308
Measure Type: Number
Unit of Measure: correlation coefficient
Free MPA (n=300) -0.004
Total MPA (n=308) -0.037
AUC MPA (n=152) -0.038
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9432
Comments Free MPA
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5177
Comments Total MPA
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6398
Comments AUC MPA
Method ANOVA
Comments [Not Specified]
28.Secondary Outcome
Title Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity
Hide Description 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.
Time Frame BL and Weeks 2, 4, 12, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; n=number of samples
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 44
Overall Number of Units Analyzed
Type of Units Analyzed: Samples
 308
Measure Type: Number
Unit of Measure: correlation coefficient
Free MPA (n=300) 0.106
Total MPA (n=308) 0.142
AUC MPA (n=152) 0.187
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0656
Comments Free MPA
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0131
Comments Total MPA
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMF Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0515
Comments AUC MPA
Method ANOVA
Comments [Not Specified]
Time Frame Adverse events (AEs) were recorded throughout treatment to the safety evaluation follow up 4 weeks after treatment discontinuation, for up to 28 weeks.
Adverse Event Reporting Description The safety assessment population included all eligible participants who received at least 1 dose of study treatment.
 
Arm/Group Title MMF Monotherapy
Hide Arm/Group Description 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.
All-Cause Mortality
MMF Monotherapy
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
MMF Monotherapy
Affected / at Risk (%)
Total   20/45 (44.44%) 
Blood and lymphatic system disorders   
Leucopenia * 1  1/45 (2.22%) 
Lymphocele * 1  15/45 (33.33%) 
Gastrointestinal disorders   
Vomiting * 1  1/45 (2.22%) 
General disorders   
Edema of the left leg * 1  1/45 (2.22%) 
Infections and infestations   
CMV infection * 1  3/45 (6.67%) 
Infection due to Legionella and Pseudomonas * 1  1/45 (2.22%) 
Sepsis * 1  1/45 (2.22%) 
Proteus mirabilis infection * 1  1/45 (2.22%) 
Gastrointestinal infection * 1  1/45 (2.22%) 
Injury, poisoning and procedural complications   
Acute rejection * 1  3/45 (6.67%) 
Acute vascular and interstitial rejection * 1  1/45 (2.22%) 
Investigations   
Increase in creatinine * 1  2/45 (4.44%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Prostatic adenocarcinoma * 1  1/45 (2.22%) 
Carcinoma of the bladder * 1  1/45 (2.22%) 
Renal and urinary disorders   
Acute renal failure * 1  1/45 (2.22%) 
Tubulitis * 1  1/45 (2.22%) 
Ureteral stenosis * 1  1/45 (2.22%) 
Urinary anastomotic leak * 1  1/45 (2.22%) 
Acute tubular necrosis * 1  2/45 (4.44%) 
Hydronephrosis * 1  1/45 (2.22%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, WHO Guidelines
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
MMF Monotherapy
Affected / at Risk (%)
Total   43/45 (95.56%) 
Blood and lymphatic system disorders   
Leukopenia * 1  13/45 (28.89%) 
Anaemia * 1  10/45 (22.22%) 
Lymphocele * 1  1/45 (2.22%) 
Antithrombin III deficiency * 1  2/45 (4.44%) 
Thrombocytopenia * 1  2/45 (4.44%) 
Iron deficiency anaemia * 1  1/45 (2.22%) 
Lymphocytopenia * 1  1/45 (2.22%) 
Acidosis * 1  1/45 (2.22%) 
Coagulopathy * 1  1/45 (2.22%) 
Cardiac disorders   
Angina pectoris * 1  1/45 (2.22%) 
Erythema * 1  1/45 (2.22%) 
Tachycardia * 1  1/45 (2.22%) 
Gastrointestinal disorders   
Vomiting * 1  5/45 (11.11%) 
Diarrhoea * 1  7/45 (15.56%) 
Abdominal pain * 1  2/45 (4.44%) 
Gastritis * 1  1/45 (2.22%) 
Gastritis erosive * 1  1/45 (2.22%) 
Gingival hyperplasia * 1  1/45 (2.22%) 
Haemorrhoids * 1  1/45 (2.22%) 
Dyspepsia * 1  1/45 (2.22%) 
Nausea * 1  1/45 (2.22%) 
Stomatitis * 1  1/45 (2.22%) 
Anal fissure * 1  1/45 (2.22%) 
Intra-abdominal haematoma * 1  1/45 (2.22%) 
Oral herpes * 1  1/45 (2.22%) 
General disorders   
Pyrexia * 1  12/45 (26.67%) 
Oedema peripheral * 1  4/45 (8.89%) 
Asthenia * 1  1/45 (2.22%) 
Hearing impaired * 1  1/45 (2.22%) 
Ear pain * 1  1/45 (2.22%) 
Pharyngolaryngeal pain * 1  1/45 (2.22%) 
Hepatobiliary disorders   
Cholestasis * 1  1/45 (2.22%) 
Lipidosis * 1  1/45 (2.22%) 
Infections and infestations   
Urinary tract infection * 1  22/45 (48.89%) 
Cytomegalovirus infection * 1  9/45 (20.00%) 
Catheter related infection * 1  1/45 (2.22%) 
Tracheitis * 1  1/45 (2.22%) 
Urethritis * 1  1/45 (2.22%) 
Cytomegalovirus viraemia * 1  1/45 (2.22%) 
Injury, poisoning and procedural complications   
Post-procedural haemorrhage * 1  1/45 (2.22%) 
Investigations   
Blood creatinine increased * 1  8/45 (17.78%) 
Blood cholesterol increased * 1  3/45 (6.67%) 
White blood cell count decreased * 1  2/45 (4.44%) 
Alanine aminotransferase increased * 1  1/45 (2.22%) 
Blood bilirubin increased * 1  1/45 (2.22%) 
Metabolism and nutrition disorders   
Hypokalaemia * 1  8/45 (17.78%) 
Hyperuricaemia * 1  7/45 (15.56%) 
Hypercholesterolemia * 1  4/45 (8.89%) 
Hyperlipemia * 1  3/45 (6.67%) 
Hypocalcaemia * 1  2/45 (4.44%) 
Diabetes mellitus * 1  1/45 (2.22%) 
Iron deficiency * 1  1/45 (2.22%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  1/45 (2.22%) 
Myalgia * 1  1/45 (2.22%) 
Myopathy * 1  1/45 (2.22%) 
Rhabdomyolysis * 1  1/45 (2.22%) 
Nervous system disorders   
Headache * 1  2/45 (4.44%) 
Paraesthesia * 1  1/45 (2.22%) 
Psychiatric disorders   
Insomnia * 1  5/45 (11.11%) 
Anxiety * 1  1/45 (2.22%) 
Renal and urinary disorders   
Renal colic * 1  2/45 (4.44%) 
Dysuria * 1  1/45 (2.22%) 
Haematuria * 1  2/45 (4.44%) 
Nocturia * 1  1/45 (2.22%) 
Glomerulosclerosis * 1  1/45 (2.22%) 
Renal artery stenosis * 1  1/45 (2.22%) 
Perirenal haematoma * 1  1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  2/45 (4.44%) 
Bronchitis * 1  1/45 (2.22%) 
Dyspnoea * 1  1/45 (2.22%) 
Skin and subcutaneous tissue disorders   
Acarodermatitis * 1  1/45 (2.22%) 
Pruritus * 1  1/45 (2.22%) 
Surgical and medical procedures   
Wound haemorrhage * 1  1/45 (2.22%) 
Operative haemorrhage * 1  1/45 (2.22%) 
Vascular disorders   
Hypertension * 1  6/45 (13.33%) 
Arteriovenous fistula * 1  1/45 (2.22%) 
Arteriovenous fistula thrombosis * 1  1/45 (2.22%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, WHO Guidelines
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
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Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01292226    
Other Study ID Numbers: ML19835
First Submitted: February 3, 2011
First Posted: February 9, 2011
Results First Submitted: October 3, 2014
Results First Posted: March 2, 2015
Last Update Posted: May 12, 2016