###  Adults

The three renal studies compared two dose levels of oral mycophenolate mofetil (1 g bid and 1.5 g bid) with azathioprine (two studies) or placebo (one study) when administered in combination with cyclosporine (Sandimmune ®†) and corticosteroids to prevent acute rejection episodes. One study also included antithymocyte globulin (ATGAM ®†) induction therapy. These studies are described by geographic location of the investigational sites. One study was conducted in the USA at 14 sites, one study was conducted in Europe at 20 sites, and one study was conducted in Europe, Canada, and Australia at a total of 21 sites. 

The primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation (defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection). Mycophenolate mofetil, when administered with antithymocyte globulin (ATGAM ®†) induction (one study) and with cyclosporine and corticosteroids (all three studies), was compared to the following three therapeutic regimens: (1) antithymocyte globulin (ATGAM ®†) induction/azathioprine/cyclosporine/corticosteroids, (2) azathioprine/cyclosporine/corticosteroids, and (3) cyclosporine/corticosteroids. 

Mycophenolate mofetil, in combination with corticosteroids and cyclosporine reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation. Table 4 and Table 5 summarize the results of these studies. These tables show (1) the proportion of patients experiencing treatment failure, (2) the proportion of patients who experienced biopsy-proven acute rejection on treatment, and (3) early termination, for any reason other than graft loss or death, without a prior biopsy-proven acute rejection episode. Patients who prematurely discontinued treatment were followed for the occurrence of death or graft loss, and the cumulative incidence of graft loss and patient death are summarized separately. Patients who prematurely discontinued treatment were not followed for the occurrence of acute rejection after termination. More patients receiving mycophenolate mofetil discontinued without prior biopsy-proven rejection, death or graft loss than discontinued in the control groups, with the highest rate in the mycophenolate mofetil 3 g/day group. Therefore, the acute rejection rates may be underestimates, particularly in the mycophenolate mofetil 3 g/day group.

The cumulative incidence of 12-month graft loss or patient death is presented below. No advantage of mycophenolate mofetil with respect to graft loss or patient death was established. Numerically, patients receiving mycophenolate mofetil 2 g/day and 3 g/day experienced a better outcome than controls in all three studies; patients receiving mycophenolate mofetil 2 g/day experienced a better outcome than mycophenolate mofetil 3 g/day in two of the three studies. Patients in all treatment groups who terminated treatment early were found to have a poor outcome with respect to graft loss or patient death at one year.

###  Pediatrics

One open-label, safety and pharmacokinetic study of mycophenolate mofetil oral suspension 600 mg/m 2bid (up to 1 g bid) in combination with cyclosporine and corticosteroids was performed at centers in the US (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection. Mycophenolate mofetil was well tolerated in pediatric patients (see ADVERSE REACTIONS), and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g bid mycophenolate mofetil capsules (see CLINICAL PHARMACOLOGY: Pharmacokinetics). The rate of biopsy-proven rejection was similar across the age groups (3 months to < 6 years, 6 years to < 12 years, 12 years to 18 years). The overall biopsy-proven rejection rate at 6 months was comparable to adults. The combined incidence of graft loss (5%) and patient death (2%) at 12 months posttransplant was similar to that observed in adult renal transplant patients.