AADAPT - Analysis of Advagraf Dose Adaptation Post Transplantation

Renal Transplantation Clinical Trial

— AADAPT  

Official title:

Prospective Pharmacokinetic and Pharmacogenetic Analysis of Advagraf After Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01435291
• Other study ID #: 11-PP-07
• Status: Completed
• Phase: Phase 4
• First received: September 15, 2011
• Last updated: July 28, 2014
• Start date: October 2011
• Est. completion date: July 2013

Study information

• Verified date: August 2011
• Source: Centre Hospitalier Universitaire de Nice
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Committee for the Protection of PersonnesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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®)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

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
• 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

Locations

Country	Name	City	State
France	Hôpital Bicêtre	Kremlin Bicêtre
France	CHU de Nice	Nice
France	CHU de Rangueil	Toulouse
France	CHRU Tours Hôpital Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC 0-24h of tacrolimus at Day 8 and Day 84		3 months	No
Secondary	AUC 24h of tacrolimus using limited samples strategies (LSS) at Day 8 and Day 84		3 months	No