Conversion From Twice-Daily Tacrolimus to Once-Daily Extended Release Tacrolimus (LCPT): The Phase III Randomized MELT Trial

Abstract

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4–15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels.

Immunosuppressive Medications

“…Aside from the direct vascular effect on renal blood flow, the potential direct nephrotoxic effects of CNI agents remain an active area of debate and research (21). To address these issues of toxicity and side effect profiles (including post-transplant diabetes), alternative formulations of tacrolimus (extended release) as well as the novel CNI voclosporin have been developed and are approved or in late-phase clinical trials in transplantation (22)(23)(24).…”

Conversion from twice daily tacrolimus capsules to once daily extended‐release tacrolimus (LCP‐Tacro): Phase 2 trial of stable liver transplant recipients

“…16 The efficacy of LCP-Tacro has been shown to be noninferior in comparison with Prograf in kidney transplantation. 17 The present study compared the pharmacokinetic (PK) and safety profile of once daily LCP-Tacro tablets to that of twice daily Prograf capsules in stable liver transplant recipients. Long-term safety and tolerability were evaluated during an open-label, 50-week extension phase.…”

Meltdose Tacrolimus Pharmacokinetics

“…The average trough concentration did not differ between the 2 treatments at 12 months (LCP-TAC, 5.19 vs TAC 5.07 ng/mL). However, the cumulative dose at 12 months was significantly lower (4.5 vs 4.8 for QD in BID; P < .001) [15].…”

“…In a study by Bunnapradist et al [15], the authors, on 162 stable KTx patients, found evidence of graft protection after 1 year of treatment with either TAC or LCP-TAC. The average trough concentration did not differ between the 2 treatments at 12 months (LCP-TAC, 5.19 vs TAC 5.07 ng/mL).…”