Safety, tolerability and pharmacokinetics of ASC10, a novel oral double prodrug of a broad-spectrum antiviral agent, β-d-N4-hydroxycytidine: results from a randomized, double-blind, placebo-controlled phase 1 study in Chinese healthy subjects

• Published in: Expert opinion on investigational drugs Vol. 33; no. 8; p. 867
• Main Authors: Liu, Jian, Zhao, Qingwei, Zhai, You, Wu, Xia, Kai, Jiejing, Ruan, Jie, Wu, Minglan, Wu, Meijia, Zhou, Zhuojun, Yan, Yuemei, Wu, Jinzi J, Qiu, Yunqing
• Format: Journal Article
• Language: English
• Published: England 01.08.2024
• Subjects: Administration, Oral; Adult; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Area Under Curve; Asian People; China; COVID-19; COVID-19 Drug Treatment; Cytidine - administration & dosage; Cytidine - adverse effects; Cytidine - analogs & derivatives; Cytidine - pharmacokinetics; Dose-Response Relationship, Drug; Double-Blind Method; Female; Healthy Volunteers; Humans; Male; Middle Aged; Prodrugs - administration & dosage; Prodrugs - adverse effects; Young Adult; China; double prodrug; pharmacokinetics; ASC10; ASC10-A; safety
• ISSN: 1744-7658
• DOI: 10.1080/13543784.2024.2377318

Considering the rise of new SARS-CoV-2 variants that have reduced the efficacy of COVID-19 vaccines, the development of new antiviral medications for the disease has become increasingly necessary. In this study, ASC10, a novel antiviral prodrug, was studied in a phase 1 trial in healthy Chinese participants. Part 1 involved 60 participants, receiving 50-800 mg ASC10 or placebo twice daily for 5.5 days. Part 2, with 12 participants, explored ASC10 dosing in the fed/fasting states. ASC10-A, the main pharmacologically active metabolite, rapidly appeared in plasma (T : 1.00-2.00 h) and decreased (t : 1.10-3.04 h) without accumulation. The C and area under the plasma concentration - time curve (AUC) of ASC10-A increased dose-dependently (50-800 mg BID) over 5.5 days, with no accumulation. The T was slightly delayed in the fed state; however, the C and AUC were similar between the fed and fasting states. Adverse events (AEs) were comparable (ASC10/placebo, 66.7%) and mostly mild (95%). ASC10 was demonstrated to be safe and well tolerated and exhibited dose-proportional exposure and minimal food effects. www.clinicaltrials.gov identifier is NCT05523141.