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Omzetting naar Envarsus om de ideale tijdpunten voor monitoring te vinden


- candidate number28448
- NTR NumberNTR6976
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR18-jan-2018
- Secondary IDsP16.321 LUMC te Leiden
- Public TitleOmzetting naar Envarsus om de ideale tijdpunten voor monitoring te vinden
- Scientific TitleConversion to tacrolimus meltdose (Envarsus), a PK guided evaluation study in stable liver transplant recipients
- ACRONYM
- hypothesis
- Healt Condition(s) or Problem(s) studiedLiver transplantation, Tacrolimus, Envarsus, Pharmocokinetic model
- Inclusion criteriaLiver transplant patients at least 6 months after transplantation
Between 18 and 70 years old
Stable on Advagraf based immunosuppressivum for at least 3 months with 2 months unchanged dose
Stable graft function
Able to give informed consent
- Exclusion criteriaInfections or complications at inclusion
Bilirubin and albumin level outside clinical reference range
Patients with GFR <30 ml/min at screening
Unstable dosing of concomitant medication with known interaction with tacrolimus
- mec approval receivedyes
- multicenter trialno
- randomisedno
- group[default]
- TypeSingle arm
- Studytypeobservational
- planned startdate 13-sep-2017
- planned closingdate1-aug-2018
- Target number of participants55
- InterventionsAdvagraf is converted to Envarsus. After 3 weeks a whole PK curve is done. After 13 weeks a limited sampling AUC is done
- Primary outcomePopulation pharmokinetic parameters tacrolimus (Envarsus)
PK dependency on CYP3A5*3, CYP3A4*22 and IL polymorphisms
- Secondary outcomeLimited PK sampling
Through concentration - AUC correlation
Changes in quality of life before and after conversion
- TimepointsInclusion: AUC advagraf + QoL
1 week after inclusion: conversion
2 weeks after conversion: whole pk curve
12 weeks after conversion: limited sampling + QoL
- Trial web site
- status[default]
- CONTACT FOR PUBLIC QUERIESDr. D.J.A.R. Moes
- CONTACT for SCIENTIFIC QUERIESDr. D.J.A.R. Moes
- Sponsor/Initiator Leiden University Medical Center (LUMC)
- Funding
(Source(s) of Monetary or Material Support)
Chiesi Pharmaceuticals
- Publications
- Brief summaryProlonged release tacrolimus (Envarsus), is a new formulation of the calcineurin inhibitor tacrolimus. This product was originally developed to improve the bioavailability of tacrolimus and to provide more consistent tacrolimus exposure. Its pharmacologically active compound tacrolimus is characterized by a narrow therapeutic window, and highly variable pharmacokinetics necessitating Therapeutic Drug Monitoring (TDM) to individualize the dose and prevent rejection or toxicity such as leukopenia and renal toxicity (3).

For patient friendly area under the curve (AUC) calculation a population PK model is required. However, at the moment there is no population pharmacokinetic model available for envarsus in contrast to other used formulations (prograft and advagraf). Genetic polymorphisms in CYP3A4 and CYP3A5 are known to cause clinically relevant variability in tacrolimus pharmacokinetics in solid organs transplantation. These genetic variants were never investigated in relationship with patients receiving Melt Dose tacrolimus (Envarsus).

Objective: To develop a population pharmacokinetic model of Envarsus in stable liver transplant recipients suitable and to evaluate the effect of CYP3A5*3, CYP3A4*22 and IL-polymorphisms of both donor and recipient on Envarsus pharmacokinetics for initial dose differentiation and compare it to the current standard Advagraf. The first secondary objective is to develop a limited sampling strategy for accurate AUC estimation of Envarsus. The second secondary objective is the evaluate quality of life of patients on both tacrolimus formulations.
Study design: An open-label, prospective, PK evaluation study
Study population: Adult liver transplant recipients aged 18 years till 70 years on a stable immunosuppressive Advagraf based regimen.
Intervention: Liver transplant recipients on a stable once daily Advagraf dose will be converted to an once daily Envarsus based regime. The dose will be determined based on the conversion ratio of 1:0.7 (SmPC of Envarsus). For the evaluation of the pharmacokinetics of Envarsus there two additional AUCs and one trough concentration of tacrolimus will be measured in addition to routine clinical care. Two weeks after conversion a full AUC measurement (T=0,1,2,3,4,6,8,12,24) will be performed to be able to assess the population pharmacokinetics of Envarsus.
- Main changes (audit trail)
- RECORD18-jan-2018 - 2-feb-2018


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