Prospective Pilot Feasibility Study Comparing Envarsus Once-a-day to Tacrolimus Twice-a-day Immunosuppressive Regimen on Drug Bioavailability in Hispanic First Time Kidney Transplant Recipients

Adequate drug dosing is essential to prevent allograft rejection and subsequent allograft
loss. Many studies have shown that serum levels of immunosuppressant medications can be
strongly influenced by the patient's genetic profile. Genetics has been shown to influence
tacrolimus drug dosing in both liver and kidney transplant recipients 1. Whether these
genetic differences influence care in clinical practice though is not known. Several genetic
influences have been identified in Hispanic patients, such as polymorphisms in Cytochrome
genes 1 and Nuclear Factor-kappa B genes 2, that might influence tacrolimus dosing and blood
levels. In a study of Hispanic children, significant correlations were found to suggest that
ethnic differences resulted in the need for higher or more frequent tacrolimus doing in
Hispanic children 3. According to the Centers for Disease Control, Hispanics are 1.5 times as
likely as non-Hispanic whites to develop ESRD 4 and Hispanics are the largest minority with
the fastest growth of ESRD in the United States 5. Therefore it is likely that the unanswered
question of whether there are differences in bioavailability of Envarsus in Hispanic patients
will become even more relevant over time. Strategies that target improved bioavailability
have the opportunity to significantly improve outcomes for all recipients of kidney
transplants. Specifically, vulnerable patient populations, such as Hispanic patients, need to
be studied to better understand the potential for altered bioavailability of
immunosuppressive medications based on inherited pharmacologic traits.

Providing patients a once-a-day option for their immunosuppressive medication dosing is
predicted to improve adherence, but whether once daily Envarsus provides adequate drug levels
in Hispanic patient groups is not known. This study will carefully evaluate drug levels as a
primary endpoint in this investigator-initiated study. Additional secondary outcomes to be
measured over the two years of the study will be allograft rejection and allograft loss. The
hypothesis of this study is that kidney transplant recipients receiving once-a-day extended
release tacrolimus (Envarsus) will have outcomes that are not inferior to those who received
twice-a-day tacrolimus during the two-year study period.

Inclusion Criteria:

- Male or Female 18 years of age or older.

- The subject is a first time stable renal transplant patients, who have received their
transplant at least 3 months before study entry.

- The subject is willing to commit to the study design.

- The subject is considered to have stable allograft function defined as no documented
rejection episodes within one month of screening.

- The subject is not currently receiving treatment with other experimental therapies
directed at their transplant.

Exclusion Criteria:

- The subject has undergone a prior organ or bone marrow transplant.

- The subject has taken any interacting/contraindicated drug determined by the
Investigator within 30 days of administration of the protocol.

- Any study drug allergies and if there are high serum donor specific antibody levels
(DSA) or a high panel reactive antibody level (PRA).

- Documented treatment of rejection within 30 days of onset of the screening visit.