AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation (AADAPT)

Prospective Pharmacokinetic and Pharmacogenetic Analysis of Advagraf After Transplantation

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®)

Study Overview

• Status: Completed
• Conditions: Renal Transplantation
• Intervention / Treatment: Drug: Advagraf Capsule; Drug: Prograf Capsule

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 Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Le Kremlin-Bicêtre, France
    • Hôpital Bicêtre
  • Nice, France, 06200
    • Chu de Nice
  • Toulouse, France
    • CHU de Rangueil
  • Tours, France
    • CHRU Tours Hopital Bretonneau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Advagraf	Drug: Advagraf 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
Active Comparator: Prograf	Drug: Prograf 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Elisabeth CASSUTO, PH, Centre Hospitalier Universitaire de Nice

Publications and helpful links

General Publications

• Kramer BK, Albano L, Banas B, Charpentier B, Backman L, Tedesco-Silva H Jr, Lehner F, Mondragon-Ramirez GA, Glyda M, Cassuto-Viguier E, Viklicky O, Mourad G, Rigotti P, Schleibner S, Kamar N. Efficacy of Prolonged- and Immediate-release Tacrolimus in Kidney Transplantation: A Pooled Analysis of Two Large, Randomized, Controlled Trials. Transplant Proc. 2017 Nov;49(9):2040-2049. doi: 10.1016/j.transproceed.2017.07.011.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: September 15, 2011
• First Posted (Estimated): September 16, 2011

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Macrolides; Lactones; Tacrolimus
• Other Study ID Numbers: 11-PP-07