PK Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®)

Tools have been developed in our unit to calculate the inter-dose AUC (Area Under Curve) of immunosuppressive drugs (ISD) based on a limited number of blood concentrations (i.e., blood samples) using Bayesian methods. Since 2005, we have implemented these tools in an expert system and made them available to the transplant community through our very successful ISBA (Immunosuppressive drugs Bayesian dose Adjustment) website.

Briefly, we first need to develop a population pharmacokinetic model using rich pharmacokinetic (PK) profiles (about 10 samples per patient over the dosing interval). The model developed can then be used for inference of ISD PK parameters in new patients using Bayesian estimation. Bayes' theorem is based on conditional probability: individual PK parameters are estimated based on the known PK parameters in the population (mean and distribution), given the dose and concentrations observed in a patient. Our previous studies have shown that a limited sampling strategy (LSS) based on 3 samples collected within the first 3 hours after drug intake can estimate adequately the interdose AUC of ISD. In the present study, the AUC0-24h and the recommended dose will be calculated using Bayesian estimators previously developed using PK data from the clinical trials run by Veloxis, and proposed to the clinicians via a dedicated website comparable with ISBA.

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Key information

Conditions

Allograft

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University Hospital of Amiens, Amiens, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Adult (≥ 18 year-old) male and female patients
Recipient of a single kidney or liver allograft
Patient transplanted for more than 2 weeks and less than 1 year at enrolment
Patient with stable Prograf® dose, defined by the following criteria:

Criterion 1: unchanged Prograf® dose for at least one week; if not, apply criterion #2
Criterion 2: unchanged Prograf® dose since the last two therapeutic drug monitorings (TDM)
Patient for whom the decision is made to switch from Prograf® to Envarsus®
Written informed consent obtained prior to any study-related procedure
Patient with tacrolimus C0 between 4 and 12 µg/L at V1
Patient with hematocrit > 27% at V1

Exclusion criteria

Patient presenting any contra-indication to tacrolimus according to the summary of product characteristics (SmPC) of Envarsus®
Recipient of any transplanted organ other than kidney or liver
Patient treated by Prograf® for less than 7 days at enrolment
Patient previously treated by any other investigational agent if it is not stopped at least 7 days prior to enrolment
Pregnant or lactating woman (based on declaration)
Patient under judicial protection
Patient 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.

Treatment and study plan

switched from Prograf® to Envarsus®

Drug

Primary outcomes

Difference between the post-switch tacrolimus steady-state AUC0-24h (V4) and the pre-switch AUC0-24h (V2).

Time frame: 3 days

The tacrolimus AUC0-24h at V2 (patient on Prograf®) will be calculated by summing the morning and the evening tacrolimus AUC0-12h.

Sponsors and collaborators

Lead sponsor

University Hospital, Limoges

Other

Registry information

Official study title

Pharmacokinetic Assessment of Tacrolimus Exposure Before and After a Switch From Twice Daily Immediate-release (Prograf®) to Once-daily Prolonged Release Tacrolimus (Envarsus®)

Acronym: ENVARSWITCH

Important dates

Study start: 2016
Primary completion: 2020
Study completion: 2020
First posted: Aug 30, 2016
Registry last updated: Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed