AUTHOR=Budde Klemens , Rostaing Lionel , Maggiore Umberto , Piotti Giovanni , Surace Daniela , Geraci Silvia , Procaccianti Claudio , Nicolini Gabriele , Witzke Oliver , Kamar Nassim , Albano Laetitia , Büchler Matthias , Pascual Julio , Gutiérrez-Dalmau Alex , Kuypers Dirk , Wekerle Thomas , Głyda Maciej , Carmellini Mario , Tisone Giuseppe , Midtvedt Karsten , Wennberg Lars , Grinyó Josep M. 

TITLE=Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus in de novo Kidney Transplant Patients Across Europe

JOURNAL=Transplant International

VOLUME=Volume 35 - 2021

YEAR=2022

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2021.10225

DOI=10.3389/ti.2021.10225

ISSN=1432-2277

ABSTRACT=Background: Tacrolimus is the calcineurin inhibitor of choice for preventing acute rejection episodes in kidney transplant patients. However, tacrolimus has a narrow therapeutic range that requires regular monitoring of blood concentrations to minimize toxicity. A new once-daily tacrolimus formulation, LCP-tacrolimus (LCPT), has been developed, which uses MeltDose™ drug-delivery technology to control drug release and enhance overall bioavailability. Our study compared dosing of LCPT with current standard-of-care tacrolimus (immediate-release tacrolimus [IR-Tac] or prolonged-release tacrolimus [PR-Tac]) during the 6 months following de novo kidney transplantation. Comparisons of graft function, clinical outcomes, safety, and tolerability for LCPT versus IR-Tac/PR-Tac were also performed. 
Methods: Standard immunological risk patients with end-stage renal disease who had received a de novo kidney transplant were randomized (1:1) to LCPT (N=200) or IR-Tac/PR-Tac (N=201). 
Results: Least squares (LS) mean tacrolimus total daily dose from Week 3 to Month 6 was significantly lower for LCPT than for IR-Tac/PR-Tac. Although LS mean tacrolimus trough levels were significantly higher for LCPT than IR-Tac/PR-Tac, tacrolimus trough levels remained within the standard reference range for most patients. There were no differences between the groups in treatment failure measures or safety profile. 
Conclusions: LCPT can achieve similar clinical outcomes to other tacrolimus formulations, with a lower daily dose.
(ClinicalTrials.gov number: NCT02432833)