tetano
Editor, Senior Moderator
Int J Antimicrob Agents
. 2024 Nov 8:107381.
doi: 10.1016/j.ijantimicag.2024.107381. Online ahead of print. Safety, tolerability, and pharmacokinetics of a novel anti-influenza agent ZX-7101A tablets in healthy Chinese participants: a first-in-human phase I clinical study
Junzhen Wu[SUP] 1 [/SUP], Qiong Wei[SUP] 1 [/SUP], Yi Jin[SUP] 1 [/SUP], Guoying Cao[SUP] 1 [/SUP], Jicheng Yu[SUP] 1 [/SUP], Xiaojie Wu[SUP] 1 [/SUP], Xinyi Yang[SUP] 1 [/SUP], Yilin Li[SUP] 2 [/SUP], Mei Liu[SUP] 2 [/SUP], Xiaoli Qin[SUP] 2 [/SUP], Jingwen Ai[SUP] 3 [/SUP], Yin Wang[SUP] 4 [/SUP], Wenhong Zhang[SUP] 5 [/SUP], Jing Zhang[SUP] 6 [/SUP]
Affiliations
We investigated the safety, tolerability, and pharmacokinetics of ZX-7101A tablets, a novel cap-dependent endonuclease inhibitor, in healthy participants in a first-in-human study. The single ascending dose (SAD) part included 40, 80, 160, 240, and 320 mg dose cohorts with10 participants in each dose cohort (8 participants received ZX-7101A tablets and 2 participants received placebo). The food effect (FE) part was a randomised, two-cycle, two-way crossover design, which enrolled 16 participants to receive single oral dose of 80 mg ZX-7101A tablets. ZX-7101A tablets were safe and well-tolerated in both SAD and FE studies. No participant died or experienced SAE, or withdrew prematurely. The prodrug ZX-7101A was rapidly transformed into the active ingredient ZX-7101 after single oral dose of 40 - 320 mg. The blood concentration of ZX-7101A was below the lower limit of quantification at most time points. ZX-7101 reached peak concentration about 3-4 h postdose in all dose cohorts. The elimination half-life of ZX-7101 was 83.01-125.55 h and AUC[SUB]0-24[/SUB] was 1655.4 to 11483.7 h*ng/mL. The FE part showed the high-fat meal significantly affected the exposure parameters compared to the fasted condition. The C[SUB]max[/SUB] and AUC[SUB]0-t[/SUB] of ZX-7101 under fasted condition were 1.73 and 1.78 times those under fed condition, respectively. Single oral dose of 40 mg and 80 mg ZX-7101A tablets achieved sufficient ZX-7101 exposure for effectively inhibiting influenza A and B viruses and avian influenza viruses. These findings support 40 mg and 80 mg of ZX-7101A tablets as single dose regimens for use in phase II/III clinical trials. This study was registered at chinadrugtrials.org.cn (identifier: CTR20212778).
. 2024 Nov 8:107381.
doi: 10.1016/j.ijantimicag.2024.107381. Online ahead of print. Safety, tolerability, and pharmacokinetics of a novel anti-influenza agent ZX-7101A tablets in healthy Chinese participants: a first-in-human phase I clinical study
Junzhen Wu[SUP] 1 [/SUP], Qiong Wei[SUP] 1 [/SUP], Yi Jin[SUP] 1 [/SUP], Guoying Cao[SUP] 1 [/SUP], Jicheng Yu[SUP] 1 [/SUP], Xiaojie Wu[SUP] 1 [/SUP], Xinyi Yang[SUP] 1 [/SUP], Yilin Li[SUP] 2 [/SUP], Mei Liu[SUP] 2 [/SUP], Xiaoli Qin[SUP] 2 [/SUP], Jingwen Ai[SUP] 3 [/SUP], Yin Wang[SUP] 4 [/SUP], Wenhong Zhang[SUP] 5 [/SUP], Jing Zhang[SUP] 6 [/SUP]
Affiliations
- PMID: 39522831
- DOI: 10.1016/j.ijantimicag.2024.107381
We investigated the safety, tolerability, and pharmacokinetics of ZX-7101A tablets, a novel cap-dependent endonuclease inhibitor, in healthy participants in a first-in-human study. The single ascending dose (SAD) part included 40, 80, 160, 240, and 320 mg dose cohorts with10 participants in each dose cohort (8 participants received ZX-7101A tablets and 2 participants received placebo). The food effect (FE) part was a randomised, two-cycle, two-way crossover design, which enrolled 16 participants to receive single oral dose of 80 mg ZX-7101A tablets. ZX-7101A tablets were safe and well-tolerated in both SAD and FE studies. No participant died or experienced SAE, or withdrew prematurely. The prodrug ZX-7101A was rapidly transformed into the active ingredient ZX-7101 after single oral dose of 40 - 320 mg. The blood concentration of ZX-7101A was below the lower limit of quantification at most time points. ZX-7101 reached peak concentration about 3-4 h postdose in all dose cohorts. The elimination half-life of ZX-7101 was 83.01-125.55 h and AUC[SUB]0-24[/SUB] was 1655.4 to 11483.7 h*ng/mL. The FE part showed the high-fat meal significantly affected the exposure parameters compared to the fasted condition. The C[SUB]max[/SUB] and AUC[SUB]0-t[/SUB] of ZX-7101 under fasted condition were 1.73 and 1.78 times those under fed condition, respectively. Single oral dose of 40 mg and 80 mg ZX-7101A tablets achieved sufficient ZX-7101 exposure for effectively inhibiting influenza A and B viruses and avian influenza viruses. These findings support 40 mg and 80 mg of ZX-7101A tablets as single dose regimens for use in phase II/III clinical trials. This study was registered at chinadrugtrials.org.cn (identifier: CTR20212778).