Pharmacokinetics and safety of HR17031 , a fixed‐ratio of INS068 /Noiiglutide combination, in Chinese patients with hepatic impairment

Abstract Aims To evaluate the pharmacokinetics (PK) and safety of HR17031 (a fixed‐ratio combination of INS068 and Noiiglutide) in subjects with hepatic impairment. Materials and Methods This open‐label, single‐dose, nonrandomised, parallel‐design trial enrolled 24 subjects with mild (Child–Pugh A), moderate (Child–Pugh B) and normal hepatic function ( n = 8 each). Participants received a single subcutaneous injection of HR17031 (10 U/0.024 mg). PK parameters of INS068 and Noiiglutide were determined by liquid chromatography–tandem mass spectrometry, free drug fractions were assessed by ultracentrifugation, and serum C‐peptide concentrations were measured. Safety was monitored throughout. Results PK profiles of INS068 and Noiiglutide in subjects with mild hepatic impairment were comparable to those with normal function, while modest reductions were observed in moderate impairment (INS068 AUC 0–∞ geometric mean ratio [GMR]: 0.814 [0.703–0.944]; Noiiglutide AUC 0–∞ GMR: 0.713 [0.574–0.886]). Unbound fractions of both components and C‐peptide concentrations showed no significant differences across groups. HR17031 was well tolerated, and there were no serious adverse events. Conclusions HR17031 demonstrated PK profiles of INS068 and Noiiglutide comparable between subjects with mild or moderate hepatic impairment and those with normal hepatic function, with modest reductions in moderate impairment. The treatment was well tolerated with a favourable safety profile, and no significant differences in C‐peptide concentrations were observed across groups.