AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation

Centre Hospitalier Universitaire de Nice

Status and phase

Completed

Phase 4

Conditions

Renal Transplantation

Treatments

Drug: Prograf Capsule

Drug: Advagraf Capsule

Study type

Interventional

Funder types

Other

Identifiers

NCT01435291

11-PP-07

Details and patient eligibility

About

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®)

Full 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.

Enrollment

45 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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