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

Eksperymentalny: Mycophenolate Mofetil Monotherapy

Participants received an initial dose of mycophenolate mofetil (MMF), 1 gram (g), orally (PO), twice per day (BID), within 5 days of transplant for 24 weeks. Participants also received concurrent antibody induction, cyclosporine, and corticosteroids as needed according to center's practice.

Lek: mycophenolate mofetil

1 g PO BID for 24 weeks

Inne nazwy:

• CellCept

Lek: antibody induction

According to manufacturer recommendation

Lek: Cyclosporine

According to manufacturer recommendation

Lek: corticosteroid

According to manufacturer recommendation

Percentage of Participants With Acute Rejection

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 to Rejection

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

Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)

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.

Percentage of Participants With Graft Loss

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

Percentage of Participants Surviving

Total Mycophenolate Acid (MPA) by Visit and Timepoint

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.

Free MPA (mcg/mL) by Visit

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

MPA Area Under the Concentration - Time Curve From Time 0 to 12 Hours (AUC0-12) (mcg/mL) by 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).

Inosine MonoPhosphate DeHydrogenase (IMPDH) Activity by Visit and Timepoint

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).

IMPDH Expression I by Visit and Timepoint

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).

IMPDH Expression II by Visit and Timepoint

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.

Interleukin 8 (IL-8) Expression by Visit and Timepoint

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.

Tumor Necrosis Factor (TNF) Expression by Visit and Timepoint

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.

Percentage of Participants With Infection

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

Percentage of Participants With Gastrointestinal Toxicities

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

Percentage of Participants With Hematologic Toxicity

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

Spearman's Rank Correlation Coefficient Between MPA Levels and IMPDH Activity

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.

Spearman's Rank Correlation Coefficient Between IMPDH I Expression and MPA Levels

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.

Spearman's Rank Correlation Coefficient Between IMPDH I Expression and Free Fraction

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.

Spearman's Rank Correlation Coefficient Between IMPDH II Expression and MPA Levels

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.

Spearman's Rank Correlation Coefficient Between IMPDH II Expression and Free Fraction

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.

Spearman's Rank Correlation Coefficient Between IMPDH Inhibition and Risk of Acute Rejection

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.

Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Infection

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.

Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Hematologic Toxicity

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.

Spearman's Rank Correlation Coefficient Between IMPDH Expression and Risk of Gastrointestinal Toxicity

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.

Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Infection

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.

Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Hematologic Toxicity

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.

Spearman's Rank Correlation Coefficient Between MPA Levels and Risk of Gastrointestinal Toxicity

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.