[709] A Phase 2 Randomized Study of the Pharmacokinetics, Safety and Efficacy of LCP-Tacro™ Tablets Once-a-Day vs. Prograf® Capsules Twice-a-Day in De Novo Liver Transplants.

Sandy Feng, William C. Chapman, Derek DuBay. University of California San Francisco, CA; Washington University in St. Louis, MO; University of Alabama at Birmingham, AL

In a prior Phase 2 conversion study in liver transplant patients, extended-release MELTDOSE® tacrolimus (TAC) once-daily (qd) tablets (LCP-Tacro™; Veloxis Pharmaceuticals), showed 31% greater bioavailability and reduced Cmax/Cmin ratio than TAC twice-daily (bid) capsules (Prograf®; Astellas Pharmaceuticals Inc.) with good tolerability, no acute rejection (AR) or graft loss, and a robust AUC/Cmin correlation. This study evaluated PK, safety, and efficacy between LCP-Tacro qd vs. Prograf bid in de novo liver transplants.
After transplantation, patients were randomized to LCP-Tacro 0.07-0.11 mg/kg qd (0.09-0.13 mg/kg for African-Americans) or Prograf at 0.10-0.15 mg/kg/day (divided bid). Subsequent doses of both drugs were adjusted to maintain TAC trough levels of 5-20 ng/mL through Day 90 and 5-15 ng/mL thereafter. 24-hour PK profile was obtained on Days 1, 7, and 14 with trough level and efficacy/safety monitoring through 1 year.
The mITT population was: LCP-Tacro, n=29 and Prograf, n=29. Day 1 PK showed lower TAC concentrations for LCP-Tacro vs. Prograf with no significant differences in trough levels; by Days 7 and 14 systemic and peak exposure and trough levels were similar between the groups (p>0.05); degree of fluctuation was greater for Prograf vs. LCP-Tacro on Day 7 (p=0.007). Similar proportions of patients in both groups met therapeutic trough targets: Day 2: 24% LCP-Tacro, 35% Prograf; Day 7: 79% both groups; Day 14: 62% LCP-Tacro, 66% Prograf. Dose adjustments were frequent in the first 14 days and slightly greater for Prograf (mean: 4.8/patient) vs. LCP-Tacro (3.9/patient). On Day 14 there was a robust correlation between C0 and AUC for both LCP-Tacro (r=0.93) and Prograf (0.88), p<0.0001 for both groups. Two patients in each group died during the study; none were suspected to be related to study drug. There were no significant differences between groups in AEs. Incidence of biopsy-proven AR was similar in both groups (at Day 360: LCP-Tacro, n=6; Prograf, n=4). Mean change from baseline in eGFR was not significantly different between the LCP-Tacro and Prograf groups (p=0.78).
LCP-Tacro had similar safety and efficacy as Prograf in de novo liver transplants. PK outcomes were similar but fluctuation was greater for Prograf at Day 7. These results add evidence that LCP-Tacro qd may be an attractive alternative to Prograf bid.
Keywords: Liver transplantation; Immunosuppression; Dosage; Area-under-curve (AUC)

Session: Poster Session: Liver: Immunosuppression Acute / Chronic Rejection (5:30 PM-7:00 PM)
Date/Time: Saturday, June 2, 2012 - 5:30 PM
Room: Exhibit Halls C and D


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