Renal Transplantation
Conditions
Brief summary
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
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.
Interventions
DRUGAdvagraf Capsule
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
DRUGPrograf Capsule
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
Sponsors
Centre Hospitalier Universitaire de Nice
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC 0-24h of tacrolimus at Day 8 and Day 84 | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| AUC 24h of tacrolimus using limited samples strategies (LSS) at Day 8 and Day 84 | 3 months |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORElisabeth CASSUTO, PH
Centre Hospitalier Universitaire de Nice
Outcome results
None listed