Date Published: March 21, 2013
Publisher: Blackwell Publishing Ltd
Author(s): S Bunnapradist, K Ciechanowski, P West-Thielke, S Mulgaonkar, L Rostaing, B Vasudev, K Budde.
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.
Tacrolimus capsules (Prograf®, Astellas Pharma US, Inc.) are indicated for the prophylaxis of organ rejection in patients receiving liver, kidney or heart transplants. Tacrolimus twice daily has proven to be highly effective in preventing acute rejection after kidney transplantation 1 and as such is widely used as part of the immunosuppression regimen for kidney transplant recipients. The latest OPTN data indicated that 89.7% of kidney transplant recipients transplanted in 2009 received tacrolimus prior to hospital discharge and that at 1 year posttransplantation, 90.0% of patients (transplanted in 2008) were on tacrolimus 2.
The methods are briefly summarized below with a complete description available as Supporting files available online.
The results reported here are from the first phase III trial to examine the efficacy and safety of converting stable kidney transplant recipients to LCPT from tacrolimus twice daily. This open-label, randomized study in 324 stable kidney transplant recipients demonstrated that patients can be successfully converted from tacrolimus twice daily to LCPT, while maintaining efficacy and safety. By local pathology and central reading, the rates of efficacy failure were equivalent between the groups.