AZD5642和达格列净在心力衰竭和中度肾功能损害患者中的1b期随机临床试验

IF 2.1 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Macarena Paz Quintana-Hayashi PhD , Kathleen Connolly PhD , Peter Greasley PhD , Melanie Chan MS , Masood Sadaat MD , Sara Svedlund MD, PhD , Jaya Birgitte Rosenmeier MD, PhD
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引用次数: 0

摘要

AZD5462是临床开发的第一个口服选择性松弛素/胰岛素样家族肽受体1激动剂。这项机制研究的目的是研究AZD5462在钠-葡萄糖共转运蛋白2抑制剂达格列净的基础上给药对心力衰竭和中度肾功能损害患者的肾脏影响。AURORA是一项1b期、安慰剂对照、双盲、双中心研究,在2组患者中,AZD5462在达格列净的基础上作为标准治疗。约40名射血分数≤50%、中度肾功能损害的心力衰竭患者(估计肾小球滤过率为30-60 mL/min/1.73 m2,包括在内)将按1:1随机分配至AZD5462或安慰剂片,治疗期为4周。在给药AZD5462之前,所有参与者将被标准化为10mg达格列净,达格列净作为标准护理将持续到随访期结束。该研究的目的是评估AZD5462在尿钠、蛋白尿、红细胞压积、液体平衡、心肾生物标志物和全身血流动力学方面与安慰剂相比的肾脏和血流动力学影响。AZD5462的安全性和耐受性将与安慰剂在达格列净的基础上进行进一步评估。AURORA是AZD5462在达格列净治疗心力衰竭和肾功能损害患者的1b期药理学、药代动力学和安全性研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Phase 1b Randomized Clinical Trial of AZD5642 and Dapagliflozin in Patients With Heart Failure and Moderate Renal Impairment
AZD5462 is the first oral selective relaxin/insulin-like family peptide receptor 1 agonist in clinical development. The aim of this mechanistic study is to investigate the renal effects of AZD5462 when administered on top of the sodium–glucose cotransporter 2 inhibitor dapagliflozin in participants with heart failure and moderate renal impairment. AURORA is a phase 1b, placebo-controlled, double-blind, 2-centre study of AZD5462 on top of dapagliflozin as standard of care in 2 arms. Approximately 40 participants with heart failure with ejection fraction ≤50% and moderate renal impairment (estimated glomerular filtration rate of 30–60 mL/min/1.73 m2, inclusive) will be randomized 1:1 to AZD5462 or placebo tablets for a treatment period of 4 weeks. All participants will be standardized to 10 mg dapagliflozin prior to AZD5462 administration, and dapagliflozin as standard of care will continue until the end of the follow-up period. The objectives of the study are to evaluate the renal and haemodynamic effects of AZD5462 compared with placebo on top of dapagliflozin on natriuresis, albuminuria, haematocrit, fluid balance, cardiorenal biomarkers, and systemic hemodynamics. The safety and tolerability of AZD5462 will be further evaluated compared with placebo on top of dapagliflozin. AURORA is a phase 1b pharmacodynamic, pharmacokinetic, and safety study of AZD5462 on top of dapagliflozin in patients with heart failure and renal impairment.
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来源期刊
American Journal of Cardiology
American Journal of Cardiology 医学-心血管系统
CiteScore
4.00
自引率
3.60%
发文量
698
审稿时长
33 days
期刊介绍: Published 24 times a year, The American Journal of Cardiology® is an independent journal designed for cardiovascular disease specialists and internists with a subspecialty in cardiology throughout the world. AJC is an independent, scientific, peer-reviewed journal of original articles that focus on the practical, clinical approach to the diagnosis and treatment of cardiovascular disease. AJC has one of the fastest acceptance to publication times in Cardiology. Features report on systemic hypertension, methodology, drugs, pacing, arrhythmia, preventive cardiology, congestive heart failure, valvular heart disease, congenital heart disease, and cardiomyopathy. Also included are editorials, readers'' comments, and symposia.
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