Background:
Hepatitis B virus capsid assembly modulators (HBV CAMs) are promising, clinically validated therapeutic agents for the treatment of chronic hepatitis B (CHB). The safety, tolerability, and pharmacokinetic (PK) profiles of GST-HG141, a novel HBV CAM, were evaluated in healthy Chinese volunteers.
Method:
This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 300, 400, or 500 mg) study comprising a food-effect investigation (300 mg), and a multiple-ascending-dose (MAD) (100 or 200 mg BID) study.
Result:
GST-HG141 reached the maximum plasma concentration (C
max
) at 1.25–3.00 h (median T
max
). The exposure exhibited a linear increase, while the mean half-life (t
1/2
) ranged from 13.096 h to 22.121 h. The exposure of GST-HG141 (300 mg) was higher after food intake by about 2.4-fold. In the MAD study, steady-state was reached at around day 5, and the mean trough steady-state concentrations were 423 and 588 ng/mL for 50 and 100mg cohorts, respectively. The ratios of GST-HG141 accumulation were <1.5. GST-HG141 was well tolerated in healthy Chinese subjects. The rates of adverse events (AEs) in the GST-HG141 cohort did not differ from those of the placebo cohort.
Conclusion:
GST-HG141 was tolerated in healthy Chinese subjects. The safety and PK profiles of GST-HG141 support the further evaluation of its efficacy in individuals with CHB.
Coarse-grained Simulations and AFM Nanoindentation Experiments on a Hepatitis B Virus Capsid
