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

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. This phase III noninferiority conversion trial in stable renal transplant recipients demonstrates that a novel extended‐release once‐daily tacrolimus formulation is noninferior to tacrolimus twice‐daily in efficacy failure rates, has a similar safety profile, and requires lower doses to achieve target trough levels.