First-in-human study on the pharmacokinetics, safety, and tolerability of single escalating doses and multiple doses of XT1061, a novel core protein allosteric modulator, in healthy Chinese subjects
In brief
XT1061 tolerated up to 600 mg; food halves peak levels but not overall exposure
In a first-in-human study of healthy Chinese volunteers, single doses of XT1061 from 12.5 to 600 mg were well tolerated with adverse events similar to placebo, and systemic exposure rose proportionally with dose. Food reduced the peak concentration by about 50% while leaving total exposure unchanged, supporting further trials in chronic hepatitis B patients.
- Journal
- Frontiers in pharmacology (Q1)
- Published
- 30 June 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Qingmei Li, Yue Hu, Dandan Wu, Wenbo Zhen, Hong Zhang, Qi Xu, et al.
- PMID
- 42453587
- DOI
- 10.3389/fphar.2026.1860210
Why clinicians should know about it
- Picked for Hepatology (top studies of the week, 19 July 2026): First‑in‑human HBV capsid assembly modulator safety data
Abstract
OBJECTIVE: XT1061 is a newly developed oral small-molecule agent designed to promote the assembly of empty capsids devoid of pregenomic RNA, representing a potential therapeutic approach for chronic hepatitis B (CHB). This first-in-human trial aimed to assess the pharmacokinetic profile and tolerability of single ascending doses and multiple doses of XT1061 in healthy Chinese individuals. METHODS: The Phase Ia clinical study consisted of two components: a double-blind, randomized, placebo-controlled, single-ascending-dose assessment conducted under fasting conditions across dose levels ranging from 12.5 mg to 600 mg-including a food-effect evaluation at 62.5 mg-followed by a multiple-dose regimen at 250 mg administered under fasting conditions. RESULTS: XT1061 demonstrated good tolerability in healthy Chinese participants, with no notable difference in the incidence of adverse events between the XT1061 and placebo groups. Following administration, the median time to peak concentration ranged from 1.0 to 2.5 h, while the mean elimination half-life varied between 2.864 and 11.478 h. Systemic exposure exhibited an approximately dose-proportional increase. Steady-state concentrations were achieved within approximately 2 days of repeated dosing, with mean accumulation indices ranging from 1.043 to 1.333. Additionally, concomitant food intake reduced the peak plasma concentration by approximately 50%, although it had no significant impact on total systemic exposure, as measured by the area under the curve. CONCLUSION: These findings indicate that XT1061 possesses a favorable safety profile and predictable pharmacokinetics, providing a solid foundation for advancing into further clinical investigations to evaluate its efficacy and safety in patients with CHB. CLINICAL TRIAL REGISTRATION: [http://www.chinadrugtrials.org.cn/index.html], identifier [CTR20232071].
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.