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

• Published in: American journal of transplantation Vol. 13; no. 3; pp. 760 - 769
• Main Authors: Bunnapradist, S., Ciechanowski, K., West‐Thielke, P., Mulgaonkar, S., Rostaing, L., Vasudev, B., Budde, K.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01.03.2013; Elsevier Limited; Blackwell Publishing Ltd
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Brief Communications; Conversion; Drug Administration Schedule; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - drug therapy; Graft Rejection - etiology; Graft Survival; Humans; immunosuppression; Immunosuppressive Agents - administration & dosage; Kidney Diseases - surgery; kidney transplantation; Kidney Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Postoperative Complications; Prognosis; Prospective Studies; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; tacrolimus; Tacrolimus - administration & dosage; Tissue, organ and graft immunology; Phase III trial; Calcineurin inhibitor; Controlled release form; Lactone; Homotransplantation; Macrolide; Conversion; Kidney; Immunomodulator; Drug conversion; Chemotherapy; Immunosuppression; Treatment; Urinary system; Tacrolimus; Surgery; Dosage form; Graft; Clinical trial; Protein synthesis inhibitor; Immunosuppressive agent; Antibacterial agent; Daily dose; Kidney transplantation
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.12035

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.