Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation (IMPAKT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03076151
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : May 30, 2018
Information provided by (Responsible Party):
University Hospital, Limoges

Brief Summary:

Tacrolimus is a calcineurin inhibitor widely used for the prevention of allograft rejection in solid organ and bone marrow transplantation. It is characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Adoport® is an immediate-release formulation of tacrolimus, to be administered twice daily. Because of a narrow therapeutic window and a better correlation between pre-dose level and effects than between dose and effect, therapeutic drug monitoring (TDM) based on trough whole blood tacrolimus concentrations is recommended for Adoport®. TDM helps to minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).

As reported in a consensus document from a consortium of European experts on tacrolimus TDM, the interdose area-under-the curve (AUC0-12h) is expected to be the best marker of tacrolimus exposure. However, tacrolimus monitoring based on full AUC0-12h is difficult to set up in routine, due to clinical constraints and the necessity of multiple samples. Calculation of the AUC0-12h using Bayesian estimation and a limited sampling strategy, i.e. a few blood samples collected during the early phase post-dose would represent an elegant solution, as already done for other tacrolimus formulations.

Furthermore, the pharmacokinetics (PK) of tacrolimus is influenced by a single nucleotide polymorphism within intron 3 of cytochrome P450 3A5 (CYP3A5). Patients who carry at least one CYP3A5*1 allele are considered to be CYP3A5 expressors (about 12% of the Caucasian population, Hapmap project) and thus require a 1.5 to 2-fold higher starting dose than CYP3A5*3/*3 carriers to reach the predefined target exposure early after transplantation. Although this polymorphism showed no impact on the performance of the Bayesian estimators previously developed for other tacrolimus formulation, the patient status for CYP3A5*3 will be considered in this pharmacokinetic study as a potential covariate in, or confounding factor of, the PK model. Specifically, owing to a 12% frequency in the White European population, about 4 patients carriers of the CYP3A5*1 allele are expected in this study; the performance of the PK model and Bayesian estimator developed will be specifically evaluated in this subgroup.

Condition or disease Intervention/treatment Phase
Transplantation Kidney Pharmacokinetic Drug: Tacrolimus monohydrate (ADOPORT®) Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Interventional Multicentre Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation
Actual Study Start Date : February 12, 2018
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Tacrolimus monohydrate (ADOPORT®)
patients with de novo Kidney Transplantation under Tacrolimus (ADOPORT®) treatment.
Drug: Tacrolimus monohydrate (ADOPORT®)
Pharmacokinetic of Tracrolimus (ADOPORT®) on 9 blood sampling by kinetics on 4 kinetics

Primary Outcome Measures :
  1. Tacrolimus bayesian estimator performance [ Time Frame: Month 3 ]
    The evaluation of Bayesian estimator performance will be based on its capacity to predict tacrolimus AUC (Area Under the Curve), expressed as the bias (%) between the predicted AUC with the PK model and the tacrolimus AUC calculated using the linear trapezoidal rule.

Secondary Outcome Measures :
  1. Tacrolimus concentrations predicted by the PK model using a limited sample strategy [ Time Frame: Month 3 ]
    The evaluation of the Bayesian estimator performance will be based on its capacity to predict, using a limited number of samples collected during the early phase post-dose, observed tacrolimus AUC0-12h measured using the non-compartmental trapezoidal method with all the time points

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subject's written informed consent of the study
  2. Male and female (>= 18 years)
  3. Recipients of a first kidney allograft
  4. Patients transplanted for less than 7 days at enrolment
  5. Patients affiliated to a social security system

Exclusion Criteria:

  1. Patients presenting any contraindication to tacrolimus according to the summary of product characteristics of Adoport®
  2. Patient presenting anti-HLA antibodies against the graft in pre-transplantation (DSA)
  3. Recipients of any transplanted organ other than the kidney
  4. Pregnant (positive BHCG test) or lactating women
  5. Women without any method of contraception, except for women with no childbearing potential (according to the guidelines of the working group, Clinical Trial Facilitation Group, related to contraception and pregnancy test in clinical trials)
  6. Patients participating in any other interventional clinical study at inclusion as well as during the whole course of the current study
  7. Patient under judicial protection
  8. Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent, or who are unwilling to comply with the study protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03076151

Contact: Pierre Marquet, MD +33555056017
Contact: Caroline Monchaud, pharm D +3355056140

Amiens Picardie University Hospital Recruiting
Amiens, France, 80054
Contact: Gabriel Choukroun, MD    +33322455455   
Principal Investigator: Gabriel Choukroun, MD         
Limoges University Hospital Recruiting
Limoges, France, 87042
Contact: Pierre Marquet, MD    +33555053017   
Principal Investigator: Marie Essig, MD         
Poitiers University Hospital Recruiting
Poitiers, France, 86000
Contact: Antoine Thierry, MD    +33549443415   
Principal Investigator: Antoine Thierry, MD         
Tours University Hospital Recruiting
Tours, France, 37000
Contact: Mathias Buchler, MD    +33247473746   
Principal Investigator: Mathias Buchler, MD         
Sponsors and Collaborators
University Hospital, Limoges
Principal Investigator: Pierre Marquet, MD University Hospital, Limoges

Responsible Party: University Hospital, Limoges Identifier: NCT03076151     History of Changes
Other Study ID Numbers: I16009 (IMPAKT)
First Posted: March 10, 2017    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Limoges:
bayesian estimators

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action