Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial

Abstract

Jaktinib is a novel Janus kinase (JAK) inhibitor, and a phase I clinical trial of single-dose Jaktinib was conducted in a population of subjects with hepatic impairment to assess the safety, tolerability, and pharmacokinetic characteristics of Jaktinib. The patients were administered orally with 100 mg Jaktinib on day 1 in all the mild hepatic impairment group (mild group, n = 8), moderate hepatic impairment group (moderate group, n = 8) and normal hepatic function group (normal group, n = 8), and the blood samples were collected for later analysis. The mild to moderate hepatic impairment affected the metabolism of Jaktinib, which may lead to accumulation of original Jaktinib. The pharmacokinetic characteristics of the metabolites (ZG0244 and ZG0245) of Jaktinib were also analyzed. The exposure of Jaktinib is approximately 2-fold in patients with mild and moderate hepatic impairment than normal hepatic function. No serious adverse events occurred. In summary, a dosage reduction is recommended for patients with mild or moderate hepatic impairment. Further investigations for the dose adjustment in mild/moderate hepatic impairment will be considered. Trial registration number: NCT04993404.