Pharmacokinetics and Safety Study of HN0037, a Novel Anti‐Human Herpes Simplex Virus Inhibitor, in Healthy Volunteers

Abstract

HN0037 is a helicase-primase inhibitor developed to treat herpes simplex virus (HSV) infection. This study evaluated the safety,tolerability,and pharmacokinetics of HN0037,following oral administration in healthy volunteers.This double-blind, placebo-controlled, phase 1 study comprised two parts. In part 1, a single escalating dose of 10, 30, 60, 120, 200, 300, and 400 mg was assessed,and the food effect was evaluated in the 200-mg cohort.In part 2,a multiple dose evaluation involving 30 and 100 mg once a day was conducted for 14 days. Following single oral doses, the systemic exposure of HN0037 increased in a proportional manner over the lower dose range (10-120 mg) and in a subproportional manner over the higher dose range (200-400 mg). Following multiple oral doses, significant drug accumulation of systemic exposure was found at steady state, and the half-life ranged 50.4-61.0 h. The food effect study results indicated that a high-fat meal had a marginal impact on HN0037's pharmacokinetics. No differences were observed in the incidence of adverse events between HN0037 and placebo groups in either study. These results demonstrate that HN0037 is safe and well-tolerated, supporting further clinical development.

Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections

“…After years of sluggish and stepwise innovations, a new and promising avenue for development has been discovered, and it may not come as a surprise that this approach is based on a new target, i.e., the viral helicase–primase. Since the first publications of inhibitors of this enzyme complex in the mid-90s, , the helicase–primase has been developed as a validated target for anti-HSV therapy. − It is the scope of the present drug annotation to describe the journey of one such drug, pritelivir (synonyms BAY 57-1293, AIC316), from its discovery through its relevant chemistry and preclinical hurdles and up to its current status as a clinical phase 3 drug.…”

“…Since the first publications of inhibitors of this enzyme complex in the mid-90s, 8 , 9 the helicase–primase has been developed as a validated target for anti-HSV therapy. 10 − 14 It is the scope of the present drug annotation to describe the journey of one such drug, pritelivir (synonyms BAY 57-1293, AIC316), from its discovery through its relevant chemistry and preclinical hurdles and up to its current status as a clinical phase 3 drug.…”