1745-P: Effects of Moderate Renal Impairment on Pharmacokinetics and Safety of Once-Weekly Insulin GZR4

Introduction and Objective: To investigate the effects of moderate renal impairment on the pharmacokinetics (PK), safety, and tolerability of once-weekly insulin GZR4. Methods: In this open-label, single-dose, parallel-group trial, 16 adults (BMI 18.5-27.9 kg/m2) were allocated to two groups: normal renal function (NRF, glomerular filtration rate [GFR] 90 to <130 mL/min; n=8) and moderate renal impairment (MRI, GFR 30 to <60 mL/min; n=8). Following a single subcutaneous administration of 3 nmol/kg GZR4, blood samples were collected up to 672 h post-dose. The primary endpoint was to assess the difference in PK of GZR4 between two groups. Results: The mean Cmax of GZR4 was comparable between two groups (MRI, 122 ng/mL versus[vs] NRF, 118 ng/mL). The MRI group exhibited a 13% higher GZR4 exposure compared to the NRF group (AUC0-last: 19924 vs 17680 ng*h/mL; AUC0-inf: 20076 vs 17770 ng*h/mL). The estimated geometric mean difference ratio (90% CI) for Cmax, AUC0-last, and AUC0-inf were 101.22% (80.43%, 127.39%), 113.18% (96.42%, 132.86%), and 113.45% (96.69%, 133.12%), respectively. The safety profiles of the two groups were comparable, with one level 1 hypoglycemia reported in the MRI group, which recovered following glucose treatment. No serious adverse events or discontinuations occurred. Conclusion: Moderate renal impairment had no significant impact on the exposure and safety of GZR4. Thus, no specific dose adjustment of GZR4 is required in individuals with moderate renal impairment. Disclosure J. Pan: None. W. Zhao: None. H. Shen: None. J. Zhao: None. C. Hao: None. T. Xie: None. A. He: None. J. Wang: None. J. Kolaczynski: Consultant; Current; Gan & Lee Pharmaceuticals.