一个随机的,开放的标签,第一阶段,单剂量研究,对中国成年人与升高的甘油三化物,Vupanorsen,在中国成年人
Xiaojie Wu1, Jicheng Yu1, Beikang Ge2
1Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, China.
Drugs in R&D
|July 1, 2024
概括
在中国成年人中,Vupanorsen有效降低了高水平的甘油三和异位性脂蛋白. 该药物表现出良好的安全性,与之前在其他人群中进行的研究一致.
科学领域:
- 药理学和治疗学 药理学和治疗学
- 心血管疾病研究研究
- 遗传医学是一种遗传医学.
背景情况:
- 伏帕诺森是一种与GalNAc3结合的反感性寡核酸,向血管蛋白类3 (ANGPTL3) mRNA.
- 它已证明有效降低异位性脂蛋白在患有失脂血症的个体.
研究的目的:
- 评估vupanorsen的药理动力学 (PK),药理动力学 (PD) 和安全性,在健康的中国成年人中,高甘油 (TG).
- 满足中国的监管要求,并评估种族敏感性.
主要方法:
- 第一个阶段,平行队列,开放标签研究.
- 18名中国成年人患有高禁食TG (≥90毫克/分升) 接受了一次性皮下注射vupanorsen剂量 (80毫克或160毫克).
- 评估了PK参数,PD标志物 (ANGPTL3,TG,非HDL-C) 和安全性.
主要成果:
- 观察到vupanorsen的快速吸收 (Tmax: 2.0小时) 和长的终端半衰期.
- 剂量相对应的暴露 (AUC,Cmax) 从80毫克增加到160毫克.
- 在ANGPTL3 (-59.7%至-69.5%),TG (-41.9%至-52.5%) 和非HDL-C (-23.2%至 -25.4%) 中发现了显著的减少.
- 没有严重的不良事件;报告了三起轻微的,已消失的与治疗有关的不良事件.
结论:
- 中国的vupanorsen的第一个临床数据.
- 中国参与者的PK和PD参数与非中国人和日本人的参数一致.
- 在这个人群中,Vupanorsen 没有显示出任何安全问题.
相关概念视频
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
833
Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
833
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
619
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
619
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
613
Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
613
Bioavailability Study Design: Single Versus Multiple Dose Studies
388
Bioavailability studies are essential for understanding how a drug is absorbed, distributed, metabolized, and excreted in the body. These studies assess the extent and rate at which the active pharmaceutical agent becomes available at the site of action. The design of bioavailability studies can involve single-dose or multiple-dose regimens, each with distinct advantages and limitations.Single-dose studies are the preferred approach due to their simplicity and reduced drug exposure for...
388
Bioavailability Study Design: Healthy Subjects Versus Patients
252
Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
252
Pharmacogenomics: Identification of New Drug Targets
129
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
129


