Conversion to Once-Daily Extended Release MeltDose® Tacrolimus Tablets (LCP-Tacro™) from Twice-Daily Tacrolimus Capsules (Prograf®) Is Safe and Efficacious in African American Kidney Transplant Recipients: Results from a Phase III Randomized Trial.
Patricia M. West-Thielke, Kenneth A. Bodziak, David J. Cohen. University of Illinois, Chicago, IL; University Hospitals Case Medical Center, Cleveland, OH; NY-Presbyterian Hospital (Columbia), New York, NY
Enhanced pharmacokinetics, optimized dosing and noninferior efficacy have been demonstrated for extended-release MELTDOSE® tacrolimus once-daily (qd) tablets (LCP-Tacro™; Veloxis Pharmaceuticals) vs. tacrolimus (TAC) twice-daily (bid) capsules (Prograf®; Astellas Pharma) in stable kidney transplant patients. This sub-analysis evaluated efficacy and safety specifically in African American (AA) kidney transplant recipients.
Stable AA adult kidney transplant recipients (on a dose of Prograf of ≥2 mg/day unchanged for at least 30 days and TAC trough levels within the predefined therapeutic range of 4 to 15 ng/mL) were randomized to either convert to LCP-Tacro tablets qd (median time post-transplant (mTPT)=646 days) or remain on Prograf capsules bid (mTPT=455.5 days). By protocol, initial LCP-Tacro dose was 15% lower than the pre-conversion Prograf total daily dose (mean=0.08 mg/kg/day, divided twice-daily). Subsequent doses of both drugs were adjusted to maintain whole blood TAC trough levels of 4-15 ng/mL. Efficacy/safety monitoring was through 12 months.
The modified intent-to-treat population included 35 AA patients on LCP-Tacro (mean age: 51 years; 71% male) and 34 on Prograf (mean age: 48 years; 62% male). Mean TAC dose (mg/day) over the 12 month period was similar in the LCP-Tacro (7.6) and Prograf (7.3) groups; mean TAC trough levels were within the target range and similar between the drug groups throughout the study.
Graft and patient survival were 100% in both groups at 1 year. By local biopsy readings, biopsy-proven acute rejection (BPAR) was n=0 for LCP-Tacro and n=2 (6%) for Prograf (p=0.24); by blinded centralized readings, BPAR was n=0 for LCP-Tacro and n=3 (9%) for Prograf (p=0.11). The frequency of subjects with adverse events (AEs) was 89% for LCP-Tacro and 97% for Prograf (p=0.36); frequency of serious AEs was 28.6% for LCP-Tacro and 20.6% for Prograf (p=0.58).
These results demonstrate that stable AA kidney transplant recipients can be safely converted from Prograf to LCP-Tacro. A tendency for fewer BPARs was found for LCP-Tacro. Future study is needed to see if the trend for fewer BPARs translates into improved long-term clinical outcomes in the AA population, who are historically associated with poorer clinical outcomes.
Keywords: Kidney transplantation; Efficacy; Safety; African-American
Session: Poster Session: Kidney Immunosuppression: Novel Agents (5:30 PM-6:30 PM)
Date/Time: Monday, June 4, 2012 - 5:30 PM
Room: Exhibit Halls C and D