Lin Pingping, Li Chengqian, Liu Yanping, Sun Feifei, Hsieh Tsung-Han, Ma Yaping, Gao Xiaomeng, Yu Qing, Cao Yu
Clinical Trials Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Front Pharmacol. 2024 Aug 22;15:1433587. doi: 10.3389/fphar.2024.1433587. eCollection 2024.
Beinaglutide, whose active ingredient is rhGLP-1, has been widely used as a pharmacological therapy for T2DM. We explored the safety and pharmacokinetics of beinaglutide in Chinese overweight/obese volunteers to lay a foundation for clinical applications of beinaglutide as an anti-obesity drug.
An open-label, single center, multiple ascending dose phase I clinical trial was conducted in 16 overweight/obese Chinese volunteers. The plasma concentrations of beinaglutide were determined by a validated ELISA method and the pharmacokinetic parameters were estimated via non-compartmental analysis methods. Adverse events were also recorded.
Beinaglutide sequentially multiple dosing (three times daily) at different doses were generally well tolerated, without serious AEs leading to discontinuation of the trial. After multiple subcutaneous injections of different doses (0.1, 0.14 and 0.2 mg), the average blood concentration of beinaglutide with or without baseline correction showed a similar trend among different dose groups on different study days. After reaching the peak concentration around 15 min, it began to decrease, and the median of T and T was 10-15 min. The exposure increased in proportion to the dosage increment, demonstrating linear pharmacokinetic characteristics. There were no statistically significant differences in the main PK parameters and no accumulation of beinaglutide after multiple dosing. After multiple subcutaneous injections, a gender difference was observed, while no differences in BMI were found under the grouping conditions.
The safety profile and pharmacokinetic properties support further development and clinical applications of beinaglutide as an anti-obesity drug.
贝那鲁肽的活性成分是重组人胰高血糖素样肽-1（rhGLP-1），已被广泛用作2型糖尿病的药物治疗。我们探讨了贝那鲁肽在中国超重/肥胖志愿者中的安全性和药代动力学，为贝那鲁肽作为抗肥胖药物的临床应用奠定基础。
对16名超重/肥胖的中国志愿者进行了一项开放标签、单中心、多剂量递增的I期临床试验。采用经过验证的酶联免疫吸附测定（ELISA）方法测定贝那鲁肽的血浆浓度，并通过非房室分析方法估算药代动力学参数。同时记录不良事件。
不同剂量的贝那鲁肽序贯多次给药（每日三次）一般耐受性良好，无导致试验中断的严重不良事件。多次皮下注射不同剂量（0.1、0.14和0.2毫克）后，不同剂量组在不同研究日的贝那鲁肽平均血药浓度（无论是否进行基线校正）呈现相似趋势。在约15分钟左右达到峰值浓度后开始下降，达峰时间（Tmax）和消除半衰期（T1/2）的中位数为10 - 15分钟。暴露量随剂量增加成比例增加，呈现线性药代动力学特征。多次给药后主要药代动力学参数无统计学显著差异，且无贝那鲁肽蓄积现象。多次皮下注射后观察到性别差异，而在分组条件下体重指数（BMI）无差异。
安全性和药代动力学特性支持贝那鲁肽作为抗肥胖药物的进一步研发和临床应用。
