Tacrolimus capsules (Prograf®, Astellas Pharma US, Inc.) are indicated for the prophylaxis of organ rejection in patients receiving liver, kidney or heart transplants. Tacrolimus twice daily has proven to be highly effective in preventing acute rejection after kidney transplantation  and as such is widely used as part of the immunosuppression regimen for kidney transplant recipients. The latest OPTN data indicated that 89.7% of kidney transplant recipients transplanted in 2009 received tacrolimus prior to hospital discharge and that at 1 year posttransplantation, 90.0% of patients (transplanted in 2008) were on tacrolimus .
Pharmacodynamic studies have revealed that, depending on the time following transplantation, maintaining whole-blood tacrolimus trough levels between 4 ng/mL and 15 ng/mL provides sufficient protection against acute rejection and limits the occurrence of adverse events (AE) [3, 4]. The management of tacrolimus blood levels is complicated by variable patient absorption, interaction with food and concomitant medications, and the relatively low bioavailability of tacrolimus from the tacrolimus twice-daily formulation (17 ± 10%) in adult kidney transplant patients . Taken together, this may lead to variable drug exposure and high intraindividual variability, which may be associated with inferior outcomes . In addition, twice-daily dosing is not optimal as multiple-daily dosing is associated with increased risk for nonadherence [7-9], which can lead to acute rejection  and, in serious cases, graft failure .
An extended-release formulation of tacrolimus designed for once-daily administration (LCP-Tacro™ tablets [LCPT], Veloxis Pharmaceuticals, Hørsholm, Denmark) has been developed utilizing a proprietary drug delivery technology (MeltDose®, Veloxis Pharmaceuticals, Hørsholm, Denmark), which is designed to improve the bioavailability of drugs with low water solubility. This technology decreases a drug's particle size to become individual molecules, (“solid solution”) the most bioavailable form of the drug. Tacrolimus in LCPT is homogenously embedded in a vehicle system which in turn is homogenously distributed in the tablet matrix. Specifically, the controlled agglomeration of LCPT results in a granulate directly compressed into a tablet. LCPT is designed to deliver the dose throughout the GI tract, providing stable consistent absorption over the full day. Phase II studies of de novo and stable renal recipients showed reliable pharmacokinetic (PK) parameters with approximately 30% better bioavailability, only a few treatment failures, and a good safety profile (data on file). AUC24 and Cmin correlation coefficients after 7 and 14 days for de novo and converted patients were ≥0.86, demonstrating a robust correlation between LCPT tacrolimus exposure and trough levels. The primary objective of this study was to evaluate the efficacy and safety of LCPT tablets when used to replace tacrolimus twice-daily capsules for maintenance immunosuppression in adult renal transplant patients.