A Phase III Randomized Trial of Conversion to Once-Daily Extended Release Meltdose® Tacrolimus Tablets (LCP-Tacro™) from Twice-Daily Tacrolimus Capsules (Prograf®): Efficacy Results from an Analysis of Specific Patient Sub-Populations

Abstract

Introduction: Enhanced pharmacokinetics, optimized dosing, and noninferior efficacy have been demonstrated for extended-release tacrolimus (TAC) once-daily (qd) tablets (LCP-Tacro; Veloxis Pharma) vs. TAC twice-daily (bid) capsules (Prograf; Astellas Pharma). This sub-analysis evaluated whether LCP-Tacro was equally efficacious when considering ethnicity, presence of diabetes, and time post-transplant at time of conversion from Prograf to LCP-Tacro. Methods: Stable adult (mean age: 50 years; 67% male) renal transplant recipients (RTRs) (3-60 months post Tx) on Prograf (mean daily dose 2 mg/day) and TAC trough levels within the predefined therapeutic range of 4 to 15 ng/mL were randomized to either remain on Prograf bid or convert to LCP-Tacro tablets qd. By protocol, initial LCP-Tacro dose was 15% lower than the pre-conversion Prograf total daily dose; subsequent doses of both drugs were adjusted to maintain whole blood TAC trough levels of 4-15 ng/mL. Efficacy/safety monitoring of this phase III study was through 12 months. Results: The modified intent-to-treat population included 162 patients on LCP-Tacro and 162 on Prograf. Mean TAC dose (mg/day) over the 12 month period was similar in the LCP-Tacro (4.7) and Prograf (4.9) groups; mean TAC trough levels were within the target range and similar between the drug groups throughout the study. Patient survival was LCP-Tacro: 98.8% and Prograf: 99.4%; graft survival was 100.0% for both treatments. Biopsy proven acute rejection (BPAR) was infrequent in both groups (Table) and tended to be more frequent in the Prograf vs. LCP-Tacro group among African Americans (P=0.11), patients with no diabetes pre-transplantation (P=0.37), and patients who were >2 years post-transplant at time of study (P=0.23); however, no significant differences in BPAR were found between LCP-Tacro and Prograf for any of the subgroups examined.Table: [Percent of Patients with BPAR by Subgroup]Conclusion: Previously, we reported that the efficacy of LCP-Tacro was noninferior to Prograf in RTRs converted to LCP-Tacro from Prograf. These results further demonstrate the efficacy of LCP-Tacro in specific RTR populations. LCP-Tacro is efficacious both in RTRs who are in the early or long term maintenance phase post-transplantation; RTRs with or without pre-transplant diabetes, and in both African Americans and non-African Americans.