Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
The CYP3A5*1 genotype, highly prevalent in African Americans (AA), commonly necessitates higher tacrolimus (tac) dose requirements and may hinder efforts to obtain therapeutic drug levels. This may be one reason for the consistently inferior kidney transplant outcomes observed in AA recipients vs. other subpopulations, most of whom do not express CYP3A5*1 genotypes. Envarsus® XR is a novel, extended-release, once-daily, MeltDose® tablet tac formulation which, in general kidney transplant populations, has shown increased bioavailability, lower peak and less peak-to-trough fluctuation at a lower daily dose vs. twice-daily tacrolimus capsules (Prograf®), with noninferior efficacy and similar safety. The present prospective, randomized, open-label, two-sequence, three-period crossover study compares the steady state PK of once-daily Envarsus® XR to twice-daily tac capsules in stable AA kidney recipients. Preliminary data on 15 patients show that Envarsus® XR is significantly associated with lower Cmax (p<0.0001), and similar Cmin (p=.440) and AUC (p=0.416). These preliminary results suggest that the improved PK and lower total daily dose requirements associated with Envarsus® XR compared to twice-daily tac, is also applicable in AA. We plan to enroll 72 AA patients (n=36 in each group). In an effort to generate a robust mix of CYP3A5*1 and non-CYP3A5*1 expressers, we are planning to randomize to each group equal proportions of subjects requiring high (≥0.15 mg/kg/day) or low (<0.15mg/kg/day) daily maintenance tac dosing at baseline. Additional results will be available May 2015.
|Envarsus® XR||Twice-daily Tac||P-value|
|Cmax (ng/mL)||16.2 (13.6, 19.5)||26.3 (21.9, 31.6)||<0.0001|
|Cmin (ng/mL)||5.9 (5.2, 6.7)||5.6 (4.9, 6.3)||0.440|
|AUC24 (hr*ng/mL)||242.4 (212.0, 277.1)||230.8 (201.7, 264.1)||0.416|
To cite this abstract in AMA style:Trofe-Clark J, Brennan D, West-Thielke P, Milone M, Lim M, Bloom R. A Randomized Cross-Over Phase 3b Study of the Pharmacokinetics of Once-Daily Extended Release MeltDose® Tacrolimus (Envarsus® XR) Versus Twice-Daily Tacrolimus in African-Americans (ASERTAA) [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/a-randomized-cross-over-phase-3b-study-of-the-pharmacokinetics-of-once-daily-extended-release-meltdose-tacrolimus-envarsus-xr-versus-twice-daily-tacrolimus-in-african-americans-asertaa/. Accessed October 31, 2020.
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