Pharmacokinetic Comparison Of All FK-506 Formulations

Study Overview
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Brief Summary
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The purpose of the study is to compare the pharmacokinetic parameters of three different formulations of tacrolimus. Eligible patients will be treated with all three formulations in a pre-defined sequence.

Detailed Description
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The pharmacokinetic parameters T(max), C(max) and AUC(0-24) will be compared between the three formulations Envarsus XR once daily, Astagraf XL once daily and Prograf Twice daily.

Official Title
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A Steady-state Pharmacokinetic Comparison Of All FK-506 Formulations

Conditions
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Renal Failure

Intervention / Treatment
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* Drug: Prograf vs Envarsus XR vs Astagraf XL
* Drug: Prograf vs Astagraf XL vs Envarsus XR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients, males or females, of 18 years of age or above. Able to participate and willing to give written informed consent and to comply with study visits and restrictions. Able to understand English. Patients having received a primary or secondary renal transplant Exclusion Criteria: Evidence of acute rejection episode within the past three months prior to screening. Recipients of organ transplants other than kidney. Patients who are known to be HIV positive.

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prograf vs Envarsus XR vs Astagraf XL<br>Prograft capsules Twice daily for 7 days, followed by Envarsus XR tablets once daily for 7 days followed by Astagraf XL capsules once daily for 7 days. | Drug: Prograf vs Envarsus XR vs Astagraf XL<br>* prograf vs Envarsus XR vs Astagraf XL<br>* Other names: Tacrolimus;|
| Active Comparator: Prograf vs Astagraf XL vs Envarsus XR<br>Prograf capsules twice daily for 7 days followed by Astagraf XL capsules once daily for 7 days followed by Envarsus XR tablets once daily. | Drug: Prograf vs Astagraf XL vs Envarsus XR<br>* Prograf vs Astagraf XL vs Envarsus XR<br>* Other names: Tacrolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of T(Max) for Envarsus XR, Astagraf XL and Prograf. | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate T(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24. | 8 days | 
| Evaluation of C(Max) for Envarsus XR, Astagraf XL and Prograf. | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate C(max). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24. | 8 days | 
| Evaluation of AUC(0-24) for Envarsus XR, Astagraf XL and Prograf. | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling times was used to calculate AUC(0-24). Nominal time points used were: Prograf sampling strategy (21 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, and 24. Envarsus XR sampling strategy (18 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, 24, and 27. Astagraf XL sampling strategy (17 samples): Pre-dose (C0) and then 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 16, 18, 21, and 24. | 8 days |