Pharmacokinetics and Safety Study of HN0141, a Novel Anti-Human Cytomegalovirus Inhibitor, in Healthy Volunteers.

HN0141 is a human cytomegalovirus (HCMV) DNA terminase complex inhibitor being developed for prophylaxis and/or preemptive treatment of HCMV infection and diseases. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of HN0141, following oral administration in healthy volunteers. The double-blind, placebo-controlled Phase 1 study comprised Part 1, an escalating, single-dose study involving 50-, 100-, 200-, 300-, 400-, and 525-mg doses; and Part 2, a multiple-dose study over 7 days involving 50-, 100-, 200-, and 400-mg twice-daily doses. HN0141 was rapidly absorbed following oral doses, with median time to maximum concentration achieved within 1-2 hours across all doses. At doses ranging from 50 to 100 mg, the PK profile was reasonably linear, while at doses above 200 mg, the PK profile was more than proportional. The predicted therapeutic dose would be 50-200 mg twice daily, which is at a reasonable linear PK range. All exposures tested (up to 525-mg single dose and 400-mg twice-daily multiple doses) were within the no-observed-adverse-effect level defined in animal toxicity studies. There was a mild accumulation on systemic exposure at steady state, which was achieved within 72 hours of multiple twice-daily dosing. No serious or severe adverse events were reported. HN0141's PK profile favors the twice-daily dosing, which gives a smaller concentration variation during the treatment, and thus could bring a better treatment effect with sufficient convenience. These Phase 1 data in safety and PK profile warrant further drug development in both preemptive and prophylactic treatment in patients with HCMV.