Conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (LCPT): a phase 2 trial of stable renal transplant recipients

A Osama Gaber, Rita R Alloway, Kenneth Bodziak, Bruce Kaplan, Suphamai Bunnapradist, A Osama Gaber, Rita R Alloway, Kenneth Bodziak, Bruce Kaplan, Suphamai Bunnapradist

Abstract

Background: LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns.

Methods: In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21.

Results: Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. C(max) (P = 0.0001), C(max)/C(min) ratio (P < 0.001), percent fluctuation (P < 0.0001), and swing (P = 0.0004) were significantly lower and T(max) significantly (P < 0.001) longer for LCP-Tacro versus Prograf. AUC24 and C(min) correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved.

Conclusions: Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations.

Figures

FIGURE 1
FIGURE 1
Patient disposition.
FIGURE 2
FIGURE 2
Mean whole-blood tacrolimus concentration in patients on days 7, 14, and 21 versus time.
FIGURE 3
FIGURE 3
Study design.

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