Methods
PD
This is a randomized, open-label, crossover study under fasting and hyperinsulinemic-euglycemic clamp conditions in healthy Chinese subjects, which was conducted at Beijing Hospital (the clinical study site) with the approval of its Drug Clinical Trial Institutional Ethics Committee in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP), and applicable laws and regulations. All subjects involved have signed informed consent forms (ICFs).The objective of this study was to preliminarily verify whether oral insulin N11005 is a prandial insulin by assessing the PK, PD, and safety profiles of N11005. A total of 12 healthy male subjects aged 18 to 45 years were enrolled in a test group (oral insulin N11005, 300IU, p.o.; T group) and a reference group (reference drug Novolin R, 0.1 IU/Kg, i.h.; R group). This study was designed to include a 10-day screening period (Day -14 ~ -4), a 2-day preparation period (Day -3~ -1), and a 2-day treatment period: from the admission of subjects to the Clinical Site on the day prior to drug administration per cycle (Day -1) to the end of that clamp cycle (2 days in total). The next cycle of administration started after a washout period of 14 days (during which relevant examinations were performed, such as physical examinations, vital signs measurements, 12-lead electrocardiogram (ECG), hematology, blood biochemistry, and urinalysis), and then subjects entered the 7-days follow-up period.For the duration of the study, blood glucose levels were measured every 5 min within 2 h prior to and 0~4 h after drug administration, and subsequently measured every 10 min within 4~8 h after drug administration. The glucose infusion rates (GIR) were calculated. At the same time, blood samples were obtained for the measurement of insulin and C-peptide levels at the following time points: every 30 min within 2 h before administration and 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420, and 480 min post drug administration.