NCT03289650

Extended Release Tacrolimus vs. Twice-Daily Tacrolimus

Once-Daily Extended-Release Tacrolimus vs. Twice-Daily Tacrolimus: Impact on T-Cell Subpopulations and Markers of Renal Tubule-toxicity in Kidney Transplant Patients

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: Lorenzo Gallon · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The overall aim of the study is to prospectively investigate the impact of two maintenance calcineurin inhibitor immunosuppressive regimens: once-daily extended release tacrolimus and twice-daily tacrolimus on subpopulations of T and B cells and alloreactive T cells as well as on renal allograft function.

Detailed description

Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. Lifelong immunosuppressive therapies are required to prevent organ rejection. However, long term exposure to immunosuppressive therapy after kidney transplantation can place patients at risk for multiple adverse events. The optimal immunosuppressive therapy is not well established. Tacrolimus, a calcineurin inhibitor (CNI) is highly effective in preventing acute rejection after organ transplantation (2). It is used as part of the immunosuppression regimen for the majority of kidney and liver transplant recipients (3). However, treatment with current formulation of Tacrolimus generates high peaks and low troughs in drug concentrations in the blood. It is known that high exposure to CNI is associated with renal toxicities and adverse events (4). New once-daily dosage formulations are now developed with the hope of minimizing side effects while maintaining excellent outcomes (5-8). LCP-Tacro (Envarsus® XR, Veloxis Pharmaceuticals), a new once-daily formulation of tacrolimus, was approved by the FDA in 2015 for conversion from twice-daily tacrolimus in kidney transplant recipients. It is a prolonged-release tacrolimus formulation, utilizing a MeltDose drug delivery technology designed to improve the bioavailability of drugs with low water solubility (1). Recent clinical data demonstrated that once-daily LCP-Tacro has improved pharmacokinetic bioavailability, rapid achievement of therapeutic trough levels, less fluctuation and swing in whole blood concentration, non-inferior efficacy and similar safety, with lower tacrolimus dose than other tacrolimus formulations. The target population is adult recipients of immediately functioning living and deceased donor renal allografts. Immediate function will be defined as the absence of the need for hemodialysis in the first week following renal transplantation. Prospective randomized single center open label study of 2 groups of kidney transplant patients * Group 1 : standard of care (SOC) control group will receive tacrolimus twice-daily (n=25) * Group 2 : LCP-Tacro (Envarsus® XR) group will receive LCPT tablets once daily (n=25)

Conditions

• End Stage Renal Disease
• Rejection of Renal Transplant

Interventions

Type	Name	Description
DRUG	Tacrolimus	immunosuppressive agent tacrolimus, given twice-daily
DRUG	Tacrolimus Extended Release Oral Tablet [Envarsus]	immunosuppressive agent extended-release tacrolimus, given once daily

Timeline

• Start date: 2017-09-05
• Primary completion: 2021-02-23
• Completion: 2021-02-23
• First posted: 2017-09-21
• Last updated: 2023-04-10
• Results posted: 2023-04-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study