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

Study Overview
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Brief Summary
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This investigator-initiated post-marketing study will evaluate the role of Hispanic ethnicity on drug dosing of Envarsus in first-time stable renal transplant recipients. Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state (e.g., trough level at 3 months post conversion) and secondary compliance assessments will be done by pill counts at clinic visits. Secondary outcomes will be the safety of once a day dosing as well as assessment of graft rejection and graft failure. In addition, concentration/dose ratios will be analyzed. The results of this study will provide important information about dosing of once a day tacrolimus (Envarsus) in Hispanic kidney transplant patients, which represents the largest growing group of patients with End-Stage Renal Disease

Detailed Description
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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.

Official Title
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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

Conditions
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Kidney Transplant; Complications, Kidney Transplant Failure and Rejection

Intervention / Treatment
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* Drug: Envarsus
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients randomized into the study group will be prescribed Envarsus, mycophenolate and prednisone as a regimen vs. standard therapy with twice a day tacrolimus, mycophenolate and prednisone. Patients randomized to the control group will be prescribed standard immunosuppression with tacrolimus twice a day, anti-proliferative twice a day, and prednisone once a day at doses that are standard at our institution.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Envarsus<br>Study group - Envarsus once daily in addition to standard of care. | Drug: Envarsus<br>* Patients randomized into the Envarsus group will be prescribed Envarsus, mycophenolate and prednisone once daily.<br>|
| Other: Tacrolimus<br>Control group - Tacrolimus twice daily in addition to standard of care. | Drug: Tacrolimus<br>* Patients randomized to the Tacrolimus group will be prescribed Tacrolimus twice-daily with standard of care immunosuppression, anti-proliferative and prednisone once-daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tacrolimus drug levels | Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state through local lab HPLC MS/MS assays. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hispanic, First time kidney recipients