The CYP3A5 genotype is the most significant genetic factor impacting tacrolimus (tac) metabolism; expresser's of this genotype require higher tac doses to achieve therapeutic tac blood concentrations compare to non-expressers. Expression of CYP3A5*1 is most commonly found among African Americans (AA). Envarsus® XR is a novel, extended-release, once-daily, MeltDose® formulation of tac which has shown improved pharmacokinetics (PK), noninferior efficacy and similar safety in kidney transplant recipients (KTR) at a lower total daily dose vs. twice-daily tac capsules (Prograf®). A pooled analysis of data from phase 3 trials in de novo and stable black KTR showed a significantly decreased risk for treatment failure for Envarsus® XR vs. Prograf®. The primary objective of the present randomized, open-label, two sequence, three period crossover study is to compare the steady state PK of Envarsus® XR once-daily to tac capsules twice-daily (tac bid) in stable AA KTR. Secondary objectives include analyzing the impact of polymorphic genotype expression. Safety and efficacy, quality of life, and medication adherence, will also be compared between Envarsus® XR and tac bid. Planned enrollment is 72 stable AA KTR randomly assigned (1:1) to one of two sequences; Sequence 1: (n=36) 18 patients requiring <0.15mg/kg/day and 18 patients requiring ≥0.15mg/kg/day. Patients will continue on tac bid on days 1-7 then switch to Envarsus® XR (at 15% lower dose); Sequence 2: (n=36) 18 patients requiring <0.15mg/kg/day and 18 patients requiring ≥0.15mg/kg/day. Patients will receive Envarsus® XR on days 1-7 then switch back to tac bid. Patients who complete the PK treatment period may participate in an extension study where they will continue on the assigned treatment for up to 6 months. To date 30 subjects have been enrolled. Results will be available mid 2015.

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