3.2.1 Single Ascending Dose Study
Mean plasma emodepside concentration-time profiles are shown in Figure 1, and PK parameters are presented in Table 3. Across all doses and for both formulations, after single administration, emodepside concentrations were rapidly quantifiable in the plasma, starting with the first timepoint at 0.5 hours post-dose. Median tmaxin subjects in the fasting state was shorter for the LSF than for the IR tablet. Exposure, based on Cmax and AUC0-24, was dose-proportional with the LSF up to the 40 mg dose, but less than dose proportional with the IR tablet. The relative bioavailability of the conventional tablet versus the LSF was 35.0% for the 5 mg dose and 11.7% for the 20 mg dose (Table 4).
In the fed state, after a single 10 mg dose of the LSF, geometric mean Cmax and AUC0-24 were lower and median tmax was longer than after the same dose in the fasting state, indicating delayed absorption of emodepside; bioavailability over the first 24 hours post-dose was lower in the fed state as compared to fasting (Table 3).
Geometric mean t1/2 at all dose levels and for both formulations was very long, while geometric mean t1/2during the first 24 hours post-dose was much shorter. Indeed, plasma emodepside concentrations were approximately 90% lower, based on geometric mean Cmax, in the first 24 hours post-dose.