Tacrolimus C:D Ratio Measured in Renal Transplant Recipients Treated With Once-daily Prolonged-release Drugs — TaC:Drop  

Immunosuppression Clinical Trial

Official title: Multicentre, Open-label, Randomised, Two-arm, Parallel-group, Superiority Trial to Assess Bioavailability and Practicability of Two Once-daily Tacrolimus Formulations, Envarsus® Compared With Advagraf™, Administered in Kidney Transplant Recipients

Status Recruiting

Clinical Trial Summary

The goal of this clinical trial is to compare the bioavailability and practicability of two different formulations of tacrolimus in kidney transplant recipients. The main objective is to demonstrate that Envarsus® (test drug) has superior (higher) oral bioavailability compared with Advagraf™ (comparator drug) at 12 weeks after kidney transplantation. The trial also aims to compare the practicability (handling) of the two drugs using a series of pharmacokinetic parameters and to explore the relationship between drug bioavailability and long-term clinical outcomes, with a special focus on dose-dependent adverse reactions, measured until 3 years post-transplantation. The trial incorporates a pharmacokinetic sub-study designed to profile the peak tacrolimus blood concentration up to 6 hours after drug intake on the day of the 12-week study visit.

Clinical Trial Description

This clinical trial aims to compare the bioavailability and practicability of two alternative once-daily formulations of tacrolimus in patients who have received either a first or second kidney transplant and require prophylactic immunosuppressive treatment to prevent allograft rejection. Trial participants are randomised within 7 days prior to kidney transplantation surgery in a 1:1 ratio to two alternative treatment arms containing either Envarsus (test arm) or Advagraf (comparator arm) as first-line calcineurin inhibitor within a standard-of-care immunosuppressive regimen. Tacrolimus blood trough levels and drug doses are monitored at regular intervals to measure a dose-normalised trough level (concentration/dose, C/D ratio) as an estimate of tacrolimus bioavailability.

The primary objective is to demonstrate that the C/D ratio of tacrolimus measured in kidney transplant recipients treated with Envarsus® (test drug) is superior to (higher than) the C/D ratio measured in patients treated with Advagraf™ (comparator drug) at 12 weeks post-transplantation. The trial also aims to compare the practicability (handling) of these two once-daily drug formulations using a series of pharmacokinetic parameters that will measure the speed with which therapeutic blood trough levels are attained and the ease with which stable blood trough levels are maintained over time.

Secondarily, TaC:Drop aims to explore the relationship between the early C/D ratio measured at 12 weeks post-transplantation and later clinical outcomes measured until three years post-transplantation. The study aims to investigate whether a superior pharmacokinetic drug profile is associated with fewer and milder dose-dependent drug toxicities and superior kidney graft function, as measured by long-term safety and efficacy parameters.

Drug pharmacokinetics will be explored in greater detail during a sub-study designed to profile the peak blood concentration of Envarsus® and Advagraf™ at 12 weeks post-transplantation in patients who volunteer to provide three additional blood samples at two-hour intervals after drug intake on the day of the 12-week trial visit. Participation in this sub-study is voluntary and available to all trial centres and all trial patients. ;

Related Conditions & MeSH terms

• Immunosuppression

• NCT number: NCT06268769
• Study type: Interventional
• Source: University of Regensburg
• Contact: Edward K. Geissler, PhD
• Phone: +49 941 944
• Email: edward.geissler@ukr.de
• Status: Recruiting
• Phase: Phase 4
• Start date: March 9, 2024
• Completion date: September 2029