Liu Wenfang, Yang Kexu, Lin Yang, Lu Chunyan, Liu Jingyi, Zhou Huan, Wang Juan, Zhang Tianhao, Yao Lingli, Qi Huanhuan, Zhang Xiaofang, Jia Rui, Li Xiaoli, Jing Shan
Clinical Pharmacology Center, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.
Clinical Trial Center, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Bengbu, 233004, China.
Clin Pharmacokinet. 2025 May;64(5):703-713. doi: 10.1007/s40262-025-01501-8. Epub 2025 Apr 19.
DBPR108 (prusogliptin) is a novel, orally bioavailable dipeptidyl peptidase-4 (DPP-4) inhibitor. This study investigated the pharmacokinetics and pharmacodynamic characteristics of DBPR108 tablets in patients with type 2 diabetes.
In this randomized, parallel-group, open-label, phase I study, Chinese adults with type 2 diabetes, glycated hemoglobin of 7.0-9.5%, and body mass index of 19-35 kg/m were randomized 1:1:1 to once-daily DBPR108 50-, 100-, or 200-mg tablet groups. The primary endpoints included pharmacokinetic and pharmacodynamic characteristics after a single dose and multiple doses of DBPR108.
In total, 30 patients were randomized with 10 patients in each group. DBPR108 was quickly absorbed with median time to reach the maximum plasma concentration of 1.5-4 h at steady state. Exposure to DBPR108 at steady-state increased dose proportionally with mean maximum steady-state plasma DBPR108 concentration during dosage intervals of 119, 256, and 567 ng/mL in the 50-, 100-, and 200-mg groups, respectively. Accumulation ratio of DBPR108 ranged from 0.85 to 1.3, and steady state was reached after four continuous daily doses. After multiple doses of DBPR108, maximum inhibitory efficacy of DPP-4 increased with higher dose levels ranging from 62.1 to 89.4%. Active glucagon-like peptide-1 levels increased after DBPR108 administration. In addition, six patients experienced treatment-emergent adverse events without leading to treatment interruption or discontinuation.
DBPR108 was well tolerated in Chinese patients with type 2 diabetes, and both the pharmacokinetic and pharmacodynamic profiles support once-daily dosage regimens of DBPR108 in future studies.
ClinicalTrials.gov (NCT05146869); registered 23 November 2021.
DBPR108（普芦糖肽）是一种新型的口服生物利用度良好的二肽基肽酶-4（DPP-4）抑制剂。本研究调查了DBPR108片在2型糖尿病患者中的药代动力学和药效学特征。
在这项随机、平行组、开放标签的I期研究中，糖化血红蛋白为7.0-9.5%、体重指数为19-35kg/m²的中国2型糖尿病成年患者按1:1:1随机分为每日一次服用DBPR108 50mg、100mg或200mg片剂组。主要终点包括单次和多次服用DBPR108后的药代动力学和药效学特征。
总共30例患者被随机分组，每组10例。DBPR108吸收迅速，稳态时达到最大血浆浓度的中位时间为1.5-4小时。稳态时DBPR108的暴露量与剂量成比例增加，50mg、100mg和200mg组在给药间隔期间的平均最大稳态血浆DBPR108浓度分别为119、256和567ng/mL。DBPR108的蓄积比为0.85至1.3，连续每日给药四次后达到稳态。多次服用DBPR108后，DPP-4的最大抑制效力随剂量水平升高而增加，范围为62.1%至89.4%。服用DBPR108后活性胰高血糖素样肽-1水平升高。此外，6例患者出现治疗中出现的不良事件，但未导致治疗中断或停药。
DBPR108在中国2型糖尿病患者中耐受性良好，药代动力学和药效学特征均支持在未来研究中采用DBPR108每日一次的给药方案。
ClinicalTrials.gov（NCT05146869）；2021年11月23日注册。
