Table 1.

Summary of clinical studies of everolimus in renal-transplant patients

Study	Design	Number of patients	Treatments	Summary of main findings
B2016	36-month, Phase III, multicenter, randomized, parallel-group, double-blind (12 months), then open-label (24 months)	588 de novo Renal-amendment population: 236 patients	Everolimus (1.5 or 3 mg/day) vs MMF (2 g/day), in addition to CsA and steroids	At 36 months, efficacy failure rates were similar for all groups (p = NS) At 36 months, patient survival, graft survival and rejection rates were similar for everolimus 1.5 mg/day vs MMF; everolimus 3 mg/day demonstrated inferior graft survival (p = 0.0048 for everolimus 1.5 vs 3 mg/day)
B2515	36-month, Phase III, multicenter, randomized, parallel-group, double-blind for ≥12 months, then open-label	583 de novo	Everolimus (1.5 or 3 mg/day) vs MMF (2 g/day), in addition to CsA and steroids	At 36 months, efficacy failure rates were similar for all groups (p = NS) At 36 months, antibody-treated acute rejection was significantly lower for everolimus 1.5 mg/day vs MMF (p = 0.014)
B15617	36-month, Phase II, multicenter, randomized, open-label, parallel-group	111 de novo	Everolimus 3 mg/day in combination with basiliximab, steroids and either full-dose or reduced-dose CsA	Efficacy failure was significantly lower in the reduced-dose vs full-dose CsA group at 6, 12 and 36 months (p < 0.05 for all) Mean creatinine clearance was higher in the reduced-dose vs full-dose CsA group at 6 months (p = 0.009), 12 months (p = 0.007) and 36 months (p = 0.436)
US0918	6-month, exploratory, multicenter, randomized, open-label	92 de novo	Everolimus in combination with steroids, basiliximab and either low- or standard-exposure tacrolimus	Efficacy was similar between groups, with BPAR occurring in 14% of patients in each group Renal function (mean serum creatinine level and estimated GFR) was similar between groups (p = NS)
A23067	12-month, Phase III, randomized, open-label, parallel-group	237 de novo	Everolimus 1.5 vs 3 mg/day, in combination with steroids and low-exposure CsA (C2 monitoring)	After 6 months, median serum creatinine levels were 133 and 132 μmol/L in the everolimus 1.5 and 3 mg/day groups, respectively After 6 months, there were no significant differences between groups for any efficacy parameter
A23077	12-month, Phase III, randomized, open-label, parallel-group	256 de novo	Everolimus 1.5 vs 3 mg/day, in combination with steroids, low-exposure CsA (C2 monitoring) and basiliximab induction therapy (Days 0 and 4)	After 6 months, median serum creatinine levels were 130 μmol/L in both everolimus groups After 6 months, there were no significant differences between groups for any efficacy parameter
CENTRAL27	6-month, single-center, pilot	20 recipients of a first or second single renal transplant from a deceased or living donor	Patients were converted from CsA to everolimus 7 weeks post-transplant; all received basiliximab induction therapy with maintenance EC-MPS and steroids	Calculated GFR improved significantly following conversion from CsA to everolimus (p = 0.001) BPAR occurred in 3/20 (15.0%) patients during the 7 weeks post-conversion to everolimus, but all episodes were mild and reversible, with subsequent recovery of renal function Abrupt conversion from CsA to everolimus was well tolerated

Abbreviations: BPAR, biopsy-proven acute refection; CsA, cyclosporine; CNI, calcineurin inhibitor; EC-MPS, enteric-coated mycophenolate sodium; GFR, glomerular filtration rate; IL-2, interleukin-2; MMF, mycophenolate mofetil; NS, not significant.