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

Allograft Clinical Trial

— ENVARSWITCH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02882828
• Other study ID #: I160015
• Status: Recruiting
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: December 2020

Study information

• Verified date: March 2019
• Source: University Hospital, Limoges
• Contact: Pierre MARQUET, MD
• Phone: +33 555 05 60 17
• Email: pierre.marquet[@]unilim.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2020
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult (= 18 year-old) male and female patients

2. Recipient of a single kidney or liver allograft

3. Patient transplanted for more than 2 weeks and less than 1 year at enrolment

4. 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)

5. Patient for whom the decision is made to switch from Prograf® to Envarsus®

6. Written informed consent obtained prior to any study-related procedure

7. Patient with tacrolimus C0 between 4 and 12 µg/L at V1

8. Patient with hematocrit > 27% at V1

Exclusion Criteria:

1. Patient presenting any contra-indication to tacrolimus according to the summary of product characteristics (SmPC) of Envarsus®

2. Recipient of any transplanted organ other than kidney or liver

3. Patient treated by Prograf® for less than 7 days at enrolment

4. Patient previously treated by any other investigational agent if it is not stopped at least 7 days prior to enrolment

5. Pregnant or lactating woman (based on declaration)

6. Patient under judicial protection

7. 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.

Related Conditions & MeSH terms

• Allograft

Intervention

Drug:
• switched from Prograf® to Envarsus®

Locations

Country	Name	City	State
France	University Hospital of Amiens	Amiens
France	University Hospital of Bordeaux	Bordeaux
France	University Hospital of Lille	Lille
France	Limoges Hospital	Limoges
France	AP-HP	Paris
France	University Hospital of Poitiers	Poitiers
France	University Hospital of Reims	Reims
France	University Hospital of Rouen	Rouen
France	University Hospital of Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference between the post-switch tacrolimus steady-state AUC0-24h (V4) and the pre-switch AUC0-24h (V2).	The tacrolimus AUC0-24h at V2 (patient on Prograf®) will be calculated by summing the morning and the evening tacrolimus AUC0-12h.	3 days