Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial

S Bunnapradist, K Ciechanowski, P West-Thielke, S Mulgaonkar, L Rostaing, B Vasudev, K Budde, MELT investigators, Rita Alloway, Rajendra Baliga, Kenneth Bodziak, Daniel Brennan, Suphamai Bunnapradist, Laurence Chan, Javier Chapochnick-Friedmann, Gaetano Ciancio, David Cohen, Laskow David, Standon Dodson, Robert Gaston, Reginald Gohh, Devon John, Anne King, Richard Knight, Sanjay Kulkarni, Paul Kuo, Jun Lee, Herwig-Ulf Meier-Kriesche, Shamkant Mulgaonkar, Kumar Mysore, Bobby Nibhanupudy, Charles Nolan, Oleh Pankewycz, Martha Pavlakis, John Pirsch, Steven Steinberg, Karin True, Brahm Vasudev, Patricia West-Thielke, Carlos Zayas, Diego Cantarovich, Georges Mourad, Lionel Rostaing, Klemens Budde, Jens Lutz, Kazimierz Ciechanowski, Michal Ciszek, Michal Nowicki, Josep Maria Grinyó Boira, Juan Carlos Ruiz San Millan, Carme Facundomolas, Alan Jardine, Richard Baker, Richard Moore, S Bunnapradist, K Ciechanowski, P West-Thielke, S Mulgaonkar, L Rostaing, B Vasudev, K Budde, MELT investigators, Rita Alloway, Rajendra Baliga, Kenneth Bodziak, Daniel Brennan, Suphamai Bunnapradist, Laurence Chan, Javier Chapochnick-Friedmann, Gaetano Ciancio, David Cohen, Laskow David, Standon Dodson, Robert Gaston, Reginald Gohh, Devon John, Anne King, Richard Knight, Sanjay Kulkarni, Paul Kuo, Jun Lee, Herwig-Ulf Meier-Kriesche, Shamkant Mulgaonkar, Kumar Mysore, Bobby Nibhanupudy, Charles Nolan, Oleh Pankewycz, Martha Pavlakis, John Pirsch, Steven Steinberg, Karin True, Brahm Vasudev, Patricia West-Thielke, Carlos Zayas, Diego Cantarovich, Georges Mourad, Lionel Rostaing, Klemens Budde, Jens Lutz, Kazimierz Ciechanowski, Michal Ciszek, Michal Nowicki, Josep Maria Grinyó Boira, Juan Carlos Ruiz San Millan, Carme Facundomolas, Alan Jardine, Richard Baker, Richard Moore

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.

© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Patient disposition.
Figure 3
Figure 3
Mean tacrolimus trough levels and mean tacrolimus daily dose during study.
Figure 4
Figure 4
Tacrolimus trough levels preceding adverse event leading to discontinuation.
Figure 5
Figure 5
Mean GFR during the study.

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