AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation

NCT ID: NCT01435291

Last Updated: 2014-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-07-31

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.

Conditions

Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Advagraf

Group Type: EXPERIMENTAL

Advagraf Capsule

Intervention Type: DRUG

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

Prograf

Group Type: ACTIVE_COMPARATOR

Prograf Capsule

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisabeth CASSUTO, PH

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Nice

Locations

Hôpital Bicêtre

Le Kremlin-Bicêtre, , France

CHU de Nice

Nice, , France

CHU de Rangueil

Toulouse, , France

CHRU Tours Hôpital Bretonneau

Tours, , France

Countries

France

Other Identifiers

11-PP-07

Identifier Type: -

Identifier Source: org_study_id