AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation

Study Overview
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Brief Summary
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A pharmacokinetics and pharmacogenetics study to complement the current knowledge of tacrolimus prolonged release (Advagraf®) in the immediate post-transplantation period and at steady-state (M3 post transplantation) and to improve the optimal dose of Advagraf® based on tacrolimus AUC estimated by two Limited Samples Strategies during the first 3 months after renal transplantation. Data obtained with tacrolimus prolonged release will be compared with those of tacrolimus immediate release (Prograf®)

Detailed Description
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Multicentre open-labeled randomized pharmacokinetic (PK) and pharmacogenetic (PG) study to compare Advagraf and Prograf immediate post-transplantation (Day 8) and steady-state (Day 84) systemic exposure. Tacrolimus PK profile, tacrolimus systemic exposure assessed by Limited Samples Strategies (LSS) (i.e.: Bayesian estimators (BE) and Multilinear Regressions (MLR)), and impact of CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus PK will also be determined to improve the optimal dose of Advagraf® for kidney transplant patients.

Official Title
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Prospective Pharmacokinetic and Pharmacogenetic Analysis of Advagraf After Transplantation

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Advagraf Capsule
* Drug: Prograf Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult recipients aged between 18 to 70 Primary renal transplantation Cadaver or living transplantation or living (non HLA identical) donor with compatible ABO blood type. absence of anti-LHA antibodies in lymphocytotoxicity and Luminex Negative cross-match in cytotoxicity Negative pregnancy test for female patients of childbearing potential, and agreement to practice effective birth control during the study Exclusion Criteria: Combined transplantation Renal bigraft History of any other transplantation Receiving a graft from a non-heart-beating donor. Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation Patient who received within one month prior to study an inductor of CYP50 3A or requiring during the study an inhibitor of CYP50 3A or of P-gp. Significant, uncontrolled concomitant infections and/or severe diarrhoea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer Subject or donor known to be HIV positive Active viral hepatitis (VHB, VHC) at randomisation Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, or mycophenolate mofetil or any of the product excipients Diagnosis of new-onset malignancy prior to transplantation, with the exception of basocellular or squamous cell carcinoma of the skin which had been treated successfully. Current participation in any other clinical study Any clinical condition which, in the opinion of the investigator, would not allow safe completion of the study Patient not able to comply with the study procedures Breast-feeding mother

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advagraf<br> | Drug: Advagraf Capsule<br>* Other Names: FK506E MR4 tacrolimus modified/prolonged release Drug: MPA Solution for infusion and per os Other Name: Mycophenolate Mofetil or Mycophenolic Acid Drug: Basiliximab IV infusion Other Name: Simulect Drug: Corticosteroids per os Other Name: Methylprednisolone or equivalent<br>|
| Active Comparator: Prograf<br> | Drug: Prograf Capsule<br>* Other Names: FK506E MR4 tacrolimus Drug: MPA Solution for infusion and per os Other Name: Mycophenolate Mofetil or Mycophenolic Acid Drug: Basiliximab IV infusion Other Name: Simulect Drug: Corticosteroids per os Other Name: Methylprednisolone or equivalent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-24h of tacrolimus at Day 8 and Day 84 |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 24h of tacrolimus using limited samples strategies (LSS) at Day 8 and Day 84 |  | 3 months |