Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Sunshine Lake Pharma Co., Ltd., Dongguan, China.
Front Endocrinol (Lausanne). 2023 Jul 26;14:1172327. doi: 10.3389/fendo.2023.1172327. eCollection 2023.
To 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.
This 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.
After 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 (tGIR≈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.
The PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile.
Clinicaltrials.gov, identifier NCT04975022.
通过评估 N11005 的药代动力学（PK）、药效动力学（PD）和安全性与短效合成人胰岛素（诺和灵 R）的比较，验证 N11005 是否作为餐时胰岛素给药。
这是一项在中国健康男性志愿者中进行的随机、开放标签、单次、交叉高胰岛素-正葡萄糖钳夹研究。共有 12 名受试者入组试验组（N11005，300IU，po）和参照组（诺和灵 R，0.1IU/kg，ih），洗脱期为 14 天。所有受试者均在钳夹研究的同一天接受治疗。在每个 8 小时的钳夹周期中，测定葡萄糖输注率（GIR）、血清胰岛素和 C 肽浓度。试验注册：Clinicaltrials.gov 标识符 NCT04975022。
给药后，T 组（N11005）和 R 组（诺和灵 R）的平均血清 C 肽浓度与基线浓度的比值均低于 50%，证实了钳夹平台的稳定性。T 组（N11005）显示出更快的作用开始（tGIR≈11min）和与 R 组相当的作用持续时间，这基本上符合餐时胰岛素的特点。整个研究过程中未发生不良事件（AE），表明 N11005 和诺和灵 R 安全且耐受良好。
单次剂量 N11005 在人体中的 PD 特征与餐时胰岛素相似，具有良好的安全性特征。
Clinicaltrials.gov，标识符 NCT04975022。
