Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Capsid Assembly Modulator GST-HG141 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial

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. This...

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Published in:Antimicrobial agents and chemotherapy 2021-09, Vol.65 (10), p.e0122021
Main Authors: Li, Cuiyun, Wu, Min, Zhang, Hong, Mai, Jiajia, Yang, Lizhi, Ding, Yanhua, Niu, Junqi, Mao, John, Wu, Wenqiang, Zhang, Dong, Tang, Yanan, Yan, Wenhao
Format: Article
Language:English
Subjects:
Administration, Oral
Area Under Curve
Capsid
China
Dose-Response Relationship, Drug
Double-Blind Method
Healthy Volunteers
Hepatitis B virus - genetics
Hepatitis B, Chronic - drug therapy
Humans
Pharmacology
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Summary: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. 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 twice daily) study. GST-HG141 reached the maximum plasma concentration ( ) at 1.25 to 3.00 h (median ). The exposure exhibited a linear increase, while the mean half-life ( ) 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 100-mg cohorts, respectively. The ratios of GST-HG141 accumulation were
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.01220-21