Pharmacokinetics and pharmacodynamics of oral insulin ( ORMD ‐0801) in healthy subjects: A phase I study using hyperinsulinaemic‐euglycaemic clamp

作者：Yufei Chen, Zhuomeng Hu, Yifei Zhang, Ming Ma, Qing Lv, Jie Zhou, Jiayi Wang, Ting Shao, Jia Shi, Yingxia Zhou, Jiangjie Lu, Haiyuan Sheng, Ya Gao, Guang Ning, Weiqing Wang · 发表于：Diabetes Obesity and Metabolism · 年份：2025 · DOI：10.1111/dom.70089 · 研究领域：Diabetes Management and Research、Hyperglycemia and glycemic control in critically ill and hospitalized patients、Diabetes Treatment and Management

Abstract Aims To characterise the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an oral insulin formulation (ORMD‐0801) in healthy subjects. Materials and Methods In this phase I hyperinsulinaemic‐euglycaemic clamp study with open‐label, randomised, crossover design, 20 healthy Chinese male subjects were randomised to receive either oral ORMD ‐0801 (8 or 16 mg), followed by subcutaneous ( SC ) insulin (5 IU , Tianmailin®) or vice versa. PK and PD parameters were evaluated by assessing changes in plasma insulin levels and glucose infusion rate ( GIR ) during an 11‐h clamp procedure. Results For 16 mg oral versus SC insulin, maximum GIR (GIR max ) was 3.87 ± 1.08 versus 3.51 ± 0.52 mg/kg/min, and area under the glucose infusion rate curve from 0 to 11 h (AUC GIR0–11h ) was 26.98 ± 10.69 versus 23.74 ± 9.04 h·mg/kg/min. For 8 mg oral versus SC insulin, GIR max was 3.86 ± 1.25 versus 5.41 ± 3.05 mg/kg/min, and AUC GIR0–11h was 27.07 ± 8.43 versus 29.95 ± 7.70 h·mg/kg/min. SC‐equivalent doses were 6.53 ± 3.97 IU (16 mg) and 4.62 ± 1.13 IU (8 mg), respectively. PK analysis showed area under the insulin concentration–time curve from zero to infinite (AUC Ins0‐∞ ) of 5.47 ± 3.17 versus 7.50 ± 2.37 h·ng/mL for 16 mg oral versus SC insulin, and 4.86 ± 2.89 versus 7.85 ± 2.02 h·ng/ mL for 8 mg oral versus SC insulin, with relative bioavailability of 0.53 ± 0.25% and 0.94 ± 0.77%. Conclusions This study comprehensively describes the PK/PD characteristics of ORMD‐0801 in hea...