BalanceD-HF: A Phase III, Randomised, Double-blind Study to Evaluate the Effect of Balcinrenone/Dapagliflozin, Compared with Dapagliflozin, on the Risk of Heart Failure Events and Cardiovascular Death in Patients with Heart Failure and Impaired Kidney Function

开始日期2024-07-01

申办/合作机构

北京协和医院

[+2]

NCT06388616

/ Completed临床1期

A Phase I, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Balcinrenone

This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of balcinrenone in patients with mild and moderate hepatic impairment in comparison to a matched healthy control group.

开始日期2024-05-02

申办/合作机构

AstraZeneca PLC

NCT05884866

/ Recruiting临床2期IIT

Natriuretic-ureothelic Adaptation of Body Fluid Homeostasis During SGLT-2 Inhibition and/or Mineralocorticoid Receptor Modulation in Patients With Chronic Kidney Disease. A 4-arm, Double-blind, Double-dummy, Parallel-group, Phase 2 Study to Investigate the Mechanistic Effects of Dapagliflozin, Dapagliflozin + Balcinrenone, Balcinrenone and Placebo on Body Solute and Water Homeostasis and Energy Metabolism in Male and Female Participants Over 50 Years of Age With Chronic Kidney Disease.

The purpose of this study is to investigate the mechanistic effects of dapagliflozin 10 mg, alone or in combination with balcinrenone 150 mg, with balcinrenone 150 mg and placebo, on the way the body handles electrolytes and water content, as well as the effects these interventions may have on energy metabolism in participants with stage 3 chronic kidney disease.
The study interventions will be administered orally, daily, in addition to current therapy, for a duration of 28 days. This will allow us to maximize our ability to detect a drug effect while minimizing the drop-out rate that accompanies longer studies.
In order to understand the different mechanistic effects of these interventions on energy metabolism, the study will be conducted at two study sites. The study design and treatment allocation, treatment duration as well as sample analysis for evaluation of the primary endpoint will be identical for all participants, at both sites. Therefore, urine and plasma samples for analysis of water and electrolyte handling will be collected from all study participants at both sites.
In addition to the primary endpoint, the main study site (Nuremberg) will conduct a metabolic study to investigate the early- and late-effects of the interventions, while the second site, Marseille, will conduct an imaging sub-study to assess changes at the tissue level before and after treatment.

开始日期2023-07-13

申办/合作机构

Klinikum Nürnberg

100 项与 Balcinrenone 相关的临床结果

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100 项与 Balcinrenone 相关的转化医学

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100 项与 Balcinrenone 相关的专利（医药）

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项与 Balcinrenone 相关的文献（医药）

2025-07-01·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of balcinrenone

Article

作者: Heijer, Maria ; Bhattacharya, Chandrali S. ; Hartleib‐Geschwindner, Judith ; Pizzato, Patricia Ely ; Leonsson‐Zachrisson, Maria ; Johansson, Susanne ; Housler, Greggory ; Boca, Simina M. ; Parkinson, Joanna ; Ericsson, Hans ; Yang, Ye

Aims:

The aim of this phase 1 trial was to assess the pharmacokinetics, safety and tolerability of balcinrenone (previously AZD9977) in participants with severe renal impairment vs. those with normal renal function.

Methods:

Participants with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) not on dialysis were compared with group‐matched control participants with eGFR ≥ 90 mL/min/1.73 m2. Eligible participants received a single oral dose of 150 mg balcinrenone, and blood and urine samples were collected for analysis.

Results:

The total apparent balcinrenone clearance was 50% lower in the severe renal impairment group, resulting in an approximately two‐fold higher area under the curve (AUC) and a 1.4‐fold higher maximum observed plasma concentration in the severe renal impairment group compared with the control group. The terminal half‐life and plasma protein binding were similar in both groups. Balcinrenone was safe and well tolerated in all participants. All reported adverse events were of mild‐to‐moderate severity and not considered related to balcinrenone.

Conclusions:

Balcinrenone exposure was approximately two‐fold higher in participants with severe renal impairment compared with the group‐matched control participants. Based on linear regression analysis of total apparent balcinrenone clearance vs. baseline eGFR, the AUC exposure is predicted to be <50% higher in patients with an eGFR of 20 mL/min/1.73 m2 compared with those with an eGFR of 60 mL/min/1.73 m2. In light of these findings, no dose adjustment based on eGFR is needed in two ongoing studies that target these patients (MIRO‐CKD [NCT06350123] and BalanceD‐HF [NCT06307652]).

2025-02-01·CPT-Pharmacometrics & Systems Pharmacology

Concentration–QT modeling demonstrates that the selective mineralocorticoid receptor modulator, balcinrenone (AZD9977), does not prolong QT interval

Article

作者: Rekic, Dinko ; Dota, Corina ; Ebrahimi, Ahmad ; Sundell, Jesper ; Parkinson, Joanna ; Johansson, Susanne ; Melin, Johanna

Abstract:

Balcinrenone (AZD9977) is a selective mineralocorticoid receptor modulator in development in combination with dapagliflozin for treatment of heart failure with impaired kidney function and chronic kidney disease. A prespecified concentration–QT analysis was performed based on data from a phase I single ascending dose study prospectively designed as a thorough QT study substitute. Oral single doses of balcinrenone of 5–800 mg, plus fractionated doses of 800 and 1200 mg, were evaluated in 62 healthy male participants. Time‐matched 12‐lead digital electrocardiogram and plasma concentrations were measured pre‐dose and up to 48 h postdose in the participants. Analysis was performed using a linear mixed‐effect model, where baseline‐adjusted Fridericia‐corrected QT interval (ΔQTcF) was a dependent variable and time‐matched balcinrenone concentration an independent variable. The model fit was deemed adequate by evaluation of goodness‐of‐fit plots, and the slope of the concentration–ΔQTcF relationship was nonsignificant (−0.003 ms/μmol/L; 95% confidence interval [CI]: −0.181, 0.176). The high clinical exposure scenario was defined as the maximum concentration (2.156 μmol/L) following the highest expected therapeutic dose (40 mg once daily) under fed conditions and in presence of a strong cytochrome P450 3A4 inhibitor. Estimated baseline‐adjusted and placebo‐corrected QTcF interval (ΔΔQTcF) at this concentration was 0.35 ms (90% CI: −1.29, 2.00). Furthermore, the upper 90% ΔΔQTcF CI was estimated to be below the threshold of regulatory concern of 10 ms at all observed concentrations (up to 16.7 μmol/L). Hence, it can be concluded that balcinrenone does not induce QTcF prolongation at the high clinical exposure scenario.

2025-02-01·EUROPEAN JOURNAL OF HEART FAILURE

Can the novel aldosterone inhibiting drug balcinrenone reduce hyperkalaemia and worsening renal function compared to steroidal mineralocorticoid receptor antagonists in heart failure?

作者: Voors, Adriaan A. ; Heerspink, Hiddo J.L. ; Beldhuis, Iris E.

A review.Mineralocorticoid receptor antagonists (MRAs) are recommended for patients with HF with reduced ejection fraction (HFrEF) and may be considered for patients with a mildly reduced ejection fraction to reduce HF hospitalizations and improve survival.There is an important need for aldosterone inhibitors that have similar or better cardiac effects but less often cause hyperkalemia or WRF. In this issue of the journal, clin. data are presented of the novel selective mineralocorticoid receptor (MR) partial antagonist, balcinrenone (formerly AZD997).Thus novel aldosterone inhibiting drug balcinrenone reduce hyperkalemia and worsen renal function compared to steroidal mineralocorticoid receptor antagonists in heart failure.

项与 Balcinrenone 相关的新闻（医药）

2025-10-21

·琼约黄昏后

阿斯利康销售榜前十之一，您看得上吗？

引言：人弃我取,人取我予。基于阿斯利康国内销售前十药物，今天我们来聊聊达格列净片吧！达格列净是一种SGLT2抑制剂，它通过抑制肾脏对葡萄糖的重吸收，使过量的糖分从尿液中排出，从而降低血糖。在中国，糖尿病与心肾疾病患者基数持续膨胀，叠加治疗理念向器官保护转变，共同重塑了市场格局。达格列净的价值已超越降糖本身，其在心衰和慢性肾病领域的应用，正引领其进行一场市场价值的重估，成为药企必争的战略要地。然而，随着达格列净被纳入集采，其红海的市场角色就更加明显了。目前市场高度集中，后来者面临的挑战是不容置疑的。如果你是立项负责人，您还会选此品吗？对此，我们不如趁机来场小辩论吧！正方：原研药占96%份额，年销超65亿，20余家仿制药企面临巨大品牌壁垒。反方：集采削弱品牌优势，8.6亿片意向采购量及27亿片潜在需求为仿制药提供明确市场机遇。当然，就算辩论赢了也不代表立项一定能成功，在医药研发领域，很多时候数据也仅仅只能起到分析作用而已！不过有市场的品种怎么也比完全没有市场的能带货的~~ 同时，咱们眼光得放远来，与其红海同质化，不如寻找差异化的蓝海呢！根据目前的研发动态，也确实有多款前景广阔的新药，正从不同维度挑战达格列净的市场地位。它们不仅在降糖效果上寻求突破，更在减重、心肾保护及用药便利性上展开竞争。药物类型/名称研发企业核心特点 / 与达格列净对比口服小分子GLP-1受体激动剂降糖效果更强，兼具显著减重优势，被视为下一代重磅靶点 Orforglipron 礼来 III期研究显示，其降糖效果（HbA1c降低1.7%）优于达格列净（降低0.8%）。 HRS-7535 恒瑞医药国内首个进入III期临床的同靶点药物，头对头挑战达格列净。 HDM1002 华东医药已启动与达格列净对照的III期糖尿病临床研究。 SGLT2抑制剂同类药物在心肾保护赛道内部竞争，寻求差异化优势恩格列净勃林格殷格翰/礼来研究显示，其在改善心衰患者部分心脏舒张功能参数上优于达格列净，但临床结局无显著差异。恒格列净恒瑞医药国产创新药，已获批与DPP-4抑制剂、二甲双胍的三联疗法。新型复方制剂通过机制互补，提升疗效和患者依从性 Balcinrenone/达格列净阿斯利康阿斯利康自身在研发的升级版复方，旨在为心衰和肾功能受损患者提供优于单用达格列净的疗效。 SGLT2/DPP-4双靶点抑制剂盛世泰科等单一分子同时抑制两个关键靶点，有望实现协同降糖并减轻副作用。总结：达格列净虽陷红海，但凭借心肾获益的独特定位，可通过集采实现市场覆盖，并借剂型与渠道创新构建成本、渠道与差异化的三重竞争壁垒。

临床3期带量采购临床成功

2024-06-26

·FiercePharma

New CKD drugs are promising, but need stronger efficacy data, kidney docs say: GlobalData

In total, the chronic kidney disease market is forecast to balloon in size from $2.2 billion last year to $13.5 billion by 2033, during which time a range of new treatments are on track to make their debuts. Though a host of drugs currently under development are poised to massively expand the existing market for chronic kidney disease (CKD) treatments, they’ll need to go further to win the support of doctors, according to a new report. The segment is expected to expand at a compound annual growth rate of nearly 20% over the course of a decade, according to GlobalData’s estimates. The report comprises the seven major markets of the U.S., France, Germany, Italy, Spain, the U.K. and Japan, though GlobalData noted that the U.S. will be a disproportionately large contributor to that growth, thanks to its higher prevalence of CKD and costs of prescription medications. In total, the CKD market is forecast to balloon in size from $2.2 billion last year to $13.5 billion by 2033, during which time a range of new treatments are on track to make their debuts. Among those now in development are ProKidney’s cell therapy rilparencel, also known as React, and AstraZeneca’s combinations of zibotentan and dapagliflozin, and balcinrenone and dapagliflozin—all of which are currently in clinical trials. Meanwhile, Novo Nordisk is also exploring a potential expanded indication for Ozempic in CKD. Just last month, Novo shared results from its FLOW study of once-weekly Ozempic’s ability to reduce the risk of major kidney disease events in patients with both CKD and Type 2 diabetes. With a median follow-up period of nearly three and a half years, the study found that participants treated with the GLP-1 had an average 24% risk reduction compared to those assigned to the placebo group, and their rate of kidney function decline was “significantly slower.” Additionally, semaglutide was shown to reduce the risk of major cardiovascular events by 18% and all-cause mortality by 20%. Following that data drop, Novo confirmed that it will pursue expanded approvals for Ozempic in the U.S. and Europe by the end of this year. Despite the promising results from the studies of those and other potential new CKD therapeutics so far, according to GlobalData, many kidney doctors have yet to be convinced to shake up their existing CKD treatment standards and have “mixed views” about tacking on another drug to their patients’ current regimens. “It will be easier for new drug entrants to capture CKD market share if they offer a novel mechanism of action or help to improve compliance,” Kajal Jaddoo, senior pharma analyst at GlobalData, said in the report. “Overall, nephrologists surveyed by GlobalData have indicated that the pipeline for CKD is somewhat promising, but a significant improvement in efficacy would have to be demonstrated by any therapy for it to become either a replacement or add-on to the existing therapies.”

临床结果上市批准细胞疗法

2024-06-09

·医药观澜

10多款1类新药在中国获批临床，来自阿斯利康、信达生物、华东医药等公司

▎药明康德内容团队编辑根据中国国家药监局药品审评中心（CDE）官网数据，近两周有10多款1类新药首次获得临床试验默示许可。通过梳理，这些新药涵盖小分子新药、抗体偶联药物（ADC）、单抗、siRNA疗法等，它们拟用于治疗癌症、慢性肾病患者、化疗相关性腹泻、亨廷顿舞蹈病、痛风等。本文将对其中部分产品进行简要介绍，仅供读者参阅。图片来源：123RF 阿斯利康：balcinrenone/达格列净胶囊作用机制：盐皮质激素受体调节剂（MRM）+SGLT2抑制剂适应症：慢性肾病患者心力衰竭阿斯利康申报的balcinrenone达格列净胶囊获批临床，拟用于降低心力衰竭合并肾功能损害患者发生心力衰竭事件和心血管死亡的风险。根据阿斯利康官网资料，这是其正在开发的慢性肾病组合疗法中的一款，为盐皮质激素受体调节剂（MRM）+SGLT2抑制剂，目前在国际范围内处于3期临床研究阶段。达格列净为一款SGLT2抑制剂，已经获得美国FDA批准治疗慢性肾病（CKD）患者，阿斯利康正在临床试验中检验多种创新疗法与达格列净联用的效果，以求进一步改善CKD患者的治疗，其中balcinrenone与达格列净联用可能增强对CKD患者心力衰竭的治疗。艾伯维：budigalimab 作用机制：抗PD-1单抗适应症：肝细胞癌艾伯维申报的budigalimab获批临床，拟联合livmoniplimab治疗在一线免疫检查点抑制剂治疗后出现疾病进展的局部晚期或转移性Child-Pugh A级肝细胞癌（HCC）。根据艾伯维公开资料，ABBV-151（livmoniplimab）是其与argenx合作开发的GARP- TGF-β1人源化单克隆抗体抑制剂，正在开发用于治疗癌症；ABBV-181（budigalimab）是一种抗PD-1人源化单克隆抗体，正在开发用于与艾伯维其他分子联合治疗实体瘤和血液系统恶性肿瘤。在国际范围内，该联合疗法治疗肝癌和非小细胞肺癌处于2期临床研究阶段。汉康生技：HCB101注射液作用机制：SIRPα融合蛋白适应症：实体瘤和非霍奇金淋巴瘤根据汉康生技（HanchorBio）新闻稿，HCB101注射液是该公司管线中的第一个项目，为一个与IgG4-Fc连结、经过工程优化的SIRPα融合蛋白。它通过阻断巨噬细胞和癌细胞之间的“别吃我”信号来触发巨噬细胞的吞噬活性。研究表明，HCB101在癌细胞内及肿瘤微环境引发了明显不同的基因表现型态，表示其可能具有独特的作用机制。此前，该产品已经在美国和中国台湾地区获批临床，并自2023年4月开始开展全球多中心多地区临床试验。本次在中国获批临床，拟用于治疗晚期实体瘤及复发难治性非霍奇金淋巴瘤。派金生物：注射用重组酰化胰高血糖素样肽2类似物作用机制：GLP-2类似物适应症：化疗相关性腹泻根据派金生物新闻稿，本次获批临床的是一款重组酰化胰高血糖素样肽2（GLP-2）类似物，为一款长效重组多肽。研究表明，GLP-2类似物可以增加绒毛高度及隐窝深度，加强肠道上皮屏障，从而减轻局部炎症并改善肠道通透性，促进肠适应。派金生物新闻稿介绍，除了用于预防和治疗化疗严重腹泻外，在非临床试验中，该产品还被证明有开发成一周一次给药治疗短肠综合征、慢性肠炎等的临床价值。艾码生物：ER2001注射液作用机制：siRNA疗法适应症：早期显性亨廷顿舞蹈病根据艾码生物新闻稿介绍，ER2001注射液通过利用人体或动物体的自身器官组织作为生物反应器，在体内被“加工”成为活性形式的siRNA，并组装进入“生物反应器”同步产生的中枢神经系统靶向的内源外泌体中，经外泌体分泌“运输”到神经元细胞，可降解其中突变亨廷顿蛋白（mHTT）的mRNA，从而产生药效。该产品获批临床的适应症为早期显性亨廷顿舞蹈病（HD）。HD是一种遗传性神经系统变性病，临床表现为运动障碍、精神症状、认知障碍等。随着病程发展，疾病晚期表现为僵直、少动为主的帕金森症状，往往严重影响患者的生活质量和寿命。中美华东：注射用HDM2005 作用机制：靶向ROR1的ADC 适应症：晚期恶性肿瘤根据中美华东新闻稿介绍，注射用HDM2005是一款靶向ROR1的ADC，现有数据显示其具有良好的成药性和安全性。ROR1是一种典型的肿瘤胚胎蛋白，该靶点具有广谱抗肿瘤性，在多类肿瘤中高度表达，是潜力ADC靶点。HDM2005已经在临床前的药效学研究、药代动力学研究及安全性评价中展现出良好的抗肿瘤活性和安全性。该产品本次获批临床的适应症为晚期恶性肿瘤。加科思：JAB-30355片作用机制：p53 Y220C激活剂适应症：携带TP53 Y220C突变的晚期实体瘤 p53 Y220C突变是一种发生在p53的DNA结合域的常见突变，携带这一突变的p53难以维持稳定的DNA结合域构象，无法完成应有的DNA调控功能。JAB-30355正是加科思自主研发的一种口服生物活性小分子激活剂，拟开发用于治疗携带P53 Y220C突变的局部晚期或转移性实体瘤患者。信达生物：替古索司他片作用机制：XOI靶向小分子适应症：痛风信达生物申报的1类新药替古索司他片已经获得临床试验默示许可，拟开发治疗痛风。根据信达生物公开资料，替古索司他片（IBI128）是一款全新非嘌呤类似物——黄嘌呤氧化酶抑制剂（XOI）。信达生物于2022年12月与总部位于韩国的LG公司化学达成一项约9550万美元的合作，从而获得该产品在中国的开发和商业化权利。除了上述产品，近期还有其他1类新药获批临床，或获批针对新适应症开展临床研究，限于篇幅，此处不再一一赘述。希望这些1类新药后续临床研究进展顺利，早日取得突破，造福患者。参考资料： [1]中国国家药监局药品审评中心（CDE）官网.Retrieved June 8，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]各公司官网及公开资料本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

临床2期临床3期抗体药物偶联物siRNA

100 项与 Balcinrenone 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性肾病	临床2期	美国	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	日本	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	比利时	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	保加利亚	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	加拿大	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	捷克	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	丹麦	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	德国	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	匈牙利	AstraZeneca PLC	2021-01-26
慢性肾病	临床2期	印度	AstraZeneca PLC	2021-01-26

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适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04595370 (MIRACLE, CTgov)	临床2期	心脏衰竭 \| 慢性肾病	153	Dapagliflozin	艱糧淵窪醖網廠築願艱(築鏇餘醖網淵廠蓋鏇淵) = 廠衊醖範遞鹹窪觸遞淵窪鹽艱鏇艱築壓餘鹽蓋 (艱淵膚鏇壓網構積願夢, 夢艱廠夢構願鏇餘鹹壓 ~ 艱淵鑰衊鑰齋憲簾壓膚) 更多	-	2024-11-19
NCT03682497 (Pubmed) 人工标引	临床1期	心脏衰竭 \| 肾功能不全	68	AZD9977	蓋壓遞鹹醖鏇鬱壓築襯(膚糧製憲糧觸簾觸積鏇) = 鏇齋艱觸鑰壓觸繭艱製齋醖衊餘獵獵蓋鬱獵願 (鹽淵淵淵鹽廠製製繭築, -5.3 ~ 4.4)	积极	2022-08-15
				spironolactone	蓋壓遞鹹醖鏇鬱壓築襯(膚糧製憲糧觸簾觸積鏇) = 簾膚顧鏇選餘衊艱醖齋齋醖衊餘獵獵蓋鬱獵願 (鹽淵淵淵鹽廠製製繭築, -0.8 ~ 7.5)
NCT03435276 (Pubmed) 人工标引	临床1期	高钾血症	27	AZD9977	淵遞窪壓積繭鏇鑰餘襯(壓鑰遞壓醖簾窪衊獵簾) = 鏇餘襯觸簾襯齋築簾夢繭艱醖糧觸鹹築構廠衊 (選餘製襯憲範齋觸餘觸 )	积极	2020-03-01
				Placebo	淵遞窪壓積繭鏇鑰餘襯(壓鑰遞壓醖簾窪衊獵簾) = 鏇鏇壓襯壓築積製艱顧繭艱醖糧觸鹹築構廠衊 (選餘製襯憲範齋觸餘觸 )
NCT03682497 (ESC2019)	临床1期	射血分数保留型心力衰竭 \| 射血分数中等的心力衰竭	27	AZD9977	選觸鏇鑰網選簾遞簾鹽(獵淵網遞築夢鏇鑰遞網) = A total of 7 adverse events occurred in 4 participants (22.2%) receiving AZD9977 and 8 events occurred in 6 participants (66.7%) receiving placebo, none severe or resulting in withdrawal from the study 艱構襯繭齋鏇淵膚築顧 (淵衊觸製願糧築廠廠繭 )	-	2019-09-03
				Placebo