Clinical trial NCT01435291: AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation
Official title: Prospective Pharmacokinetic and Pharmacogenetic Analysis of Advagraf After Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplantation
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2011-09-16
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: AUC 0-24h of tacrolimus at Day 8 and Day 84
timeFrame: 3 months
Secondary outcomes:
measure: AUC 24h of tacrolimus using limited samples strategies (LSS) at Day 8 and Day 84
timeFrame: 3 months
Other outcomes:
Locations:
city: Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: Nice
country: France
facility: CHU de Nice
city: Toulouse
country: France
facility: CHU de Rangueil
city: Tours
country: France
facility: CHRU Tours Hôpital Bretonneau
Study officials:
affiliation: Centre Hospitalier Universitaire de Nice
name: Elisabeth CASSUTO, PH
role: PRINCIPAL_INVESTIGATOR
References: