AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation

Phase 4

Completed

• Conditions: Renal Transplantation
• Interventions: Drug: Advagraf Capsule; Drug: Prograf Capsule

• Registration Number: NCT01435291
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

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.

Study Timeline

• Status Verified: 2011-08
• Study First Submitted: 2011-09-15
• Study First Submitted QC: 2011-09-15
• Study First Posted: 2011-09-16
• Study Start: 2011-10
• Primary Completion: 2013-05
• Study Completion: 2013-07
• Last Update Submitted: 2014-07-28
• Last Update Posted: 2014-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Advagraf	Advagraf Capsule	-
Prograf	Prograf Capsule	-

Primary Outcome Measures

Name	Time	Method
AUC 0-24h of tacrolimus at Day 8 and Day 84	3 months

Secondary Outcome Measures

Name	Time	Method
AUC 24h of tacrolimus using limited samples strategies (LSS) at Day 8 and Day 84	3 months

Trial Locations

Locations (4)

Hôpital Bicêtre; 🇫🇷 Kremlin Bicêtre, France

CHU de Nice; 🇫🇷 Nice, France

CHRU Tours Hôpital Bretonneau; 🇫🇷 Tours, France

CHU de Rangueil; 🇫🇷 Toulouse, France