Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) in healthy subjects

Frontiers in Endocrinology

Endocrinology

Lixin Guo¹  Qi Pan¹  Xiaoxia Wang¹  Wei-Hua Hao²  Yu-Tsai Yang²  Xiaofeng Chen³  Yulei Zhuang³  Wenjia Wang³  Yuhui Huang³  Wenjia Li³  Zhijie Wang³  Li Lan³  Qinghong Zhou³  Yijie Zhou³  Juan Hong³ 

[1] Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China;INNOPHARMAX, INC., Taipei, Taiwan;Sunshine Lake Pharma Co., Ltd., Dongguan, China;

关键词: oral insulin;    pharmacokinetics;    pharmacodynamics;    safety;    healthy subjects;   

DOI  :  10.3389/fendo.2023.1172327

 received in 2023-02-23, accepted in 2023-07-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

AimsTo verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference.MethodsThis was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022.ResultsAfter administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR10%max≈11 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated.ConclusionsThe PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile.Clinical trial registrationClinicaltrials.gov, identifier NCT04975022.

【 授权许可】

Unknown   
Copyright © 2023 Pan, Wang, Li, Chen, Zhuang, Zhou, Huang, Zhou, Lan, Wang, Wang, Hong, Hao, Yang and Guo