MeltDose® is a process technology intended to enhance oral bioavailability of poorly water soluble compounds. We evaluated the transit time, pharmacokinetic (PK) profile and site of release of tacrolimus from a controlled release once-daily formulation (LCP-Tacro™) with controlled agglomeration MeltDose technology and assessed inter- and intra-subject variability. This was a single dose, 2-way, open-label, replicate design, Phase 1, pharmacoscintigraphic study. A radiolabelled 2 mg LCP-Tacro tablet was administered to the same 8 subjects on two occasions, with a 14 day washout between dosing. Blood samples and scintigraphic images were collected at 36, 48 and 72 hours post-dose. The transit of LCP-Tacro was similar on study periods 1 and 2. Initial disintegration of the formulation tended to occur in the stomach and/or proximal small bowel and complete disintegration tended to occur in the distal small bowel or colon. Correlation of T_lag values and time to initial tablet disintegration confirmed that initial drug release is likely to be via diffusion. The C_max values were similar for the two dosing periods. The mean C_max value was 3.88 ± 0.93 ng/mL for study period 1 and 3.36 ± 1.40 ng/mL for study period 2. The mean AUC_0-∞ were 149.53 ± 22.89 ng.h/mL for study period 1 and 120.40 ± 52.06 ng.h/mL for study period 2.

There were no serious or severe AEs; no subjects discontinued because of a treatment related AE. There were no clinically significant changes in vital signs or ECGs. Using Veloxis proprietary MeltDose technology in the LCP-Tacro formulation modifies the absorption characteristics in a manner that would allow for a once-daily sustained release PK profile and enhanced bioavailability.

Nigro, V.: Employee, Veloxis Pharmaceuticals. Glicklich, A.: Employee, Veloxis Pharmaceuticals. Weinberg, J.: Employee, Veloxis Pharmaceuticals.

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