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.
Signed and dated written informed consent
Adult (≥18 years old) male or female
Renal insufficiency necessitating kidney transplantation and approved to receive a first or second kidney allograft from a living or deceased organ donor
ABO blood type compatible with the donor kidney
Multi-organ transplantation
Any previous solid organ transplantation (other than a first kidney allograft)
For recipients of a second kidney transplant: loss of first kidney transplant within 2 years after transplantation owing to immunological reasons or recurrence of the underlying renal disease
Patient and/or donor is positive for HCV, HBV or HIV
Parallel
Tacrolimus Pill
DrugEnvarsus tablets dosed to achieve and maintain whole blood trough levels of tacrolimus within a therapeutic range of 5-12 ng/ml during the first 4 weeks post-transplantation, and 5-8 ng/ml thereafter.
Tacrolimus capsule
DrugAdvagraf capsules dosed to achieve and maintain whole blood trough levels of tacrolimus within a therapeutic range of 5-12 ng/ml during the first 4 weeks post-transplantation, and 5-8 ng/ml thereafter.
Dose-normalised blood trough level of tacrolimus (concentration/dose ratio)
To calculate C/D ratio, "concentration" is the blood trough level of tacrolimus measured in a blood sample collected immediately prior to drug dosing on the day of the 12-week trial visit and "dose" is the daily dose taken by the patient on the day prior to the visit. C/D ratio is measured as a surrogate for tacrolimus bioavailability (i.e. systemic exposure per mg of drug). The primary endpoint uses a blood trough level reading that is measured in a central laboratory.
Time to reach the first trough level in target range
Reaching the target range is defined as two consecutive readings within the initial target range of 5-12 ng/ml; time is measured to the date of the first in-range reading
Proportion of patients with trough levels lower, within, or higher than the target range
Mean tacrolimus trough level and inter-patient variability (range) of tacrolimus trough levels
Mean daily dose of tacrolimus and inter-patient variability (range) of tacrolimus daily dose
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Edward Geissler
Lead sponsor
University of Regensburg
Sponsor institution
Chiesi Pharmaceuticals GmbH
Collaborator
