Division of Nephrology, Department of Medicine, University of Washington, Spokane, Washington, USA.
Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.
Am J Nephrol. 2024;55(2):262-272. doi: 10.1159/000534808. Epub 2023 Oct 30.
Aldosterone synthase (AS) inhibition may overcome increased aldosterone production in response to renin-angiotensin system inhibition. BI 690517 is an AS inhibitor under investigation for chronic kidney disease (CKD).
This multinational, phase II, double-blind study (NCT05182840) investigated the efficacy and safety of daily oral BI 690517, with or without empagliflozin 10 mg, in participants with CKD. The primary endpoint was change from baseline in urine albumin:creatinine ratio (UACR) at week 14. Between February 18, 2022, and December 30, 2022, 714 adults already treated by angiotensin-converting enzyme inhibitor (30.5%) or angiotensin receptor blocker (69.8%) were randomized (1:1) to an 8-week run-in to assign background empagliflozin (n = 356) or placebo (n = 358). Participants in each group were then randomized (1:1:1:1) to a 14-week treatment period with BI 690517 (3 mg, 10 mg, or 20 mg) or placebo. Of the 714 participants who entered run-in, 586 were randomized to the treatment period. They were predominantly men (66.6%) of white race (58.4%) with a mean (standard deviation [SD]) age of 63.8 (11.3) years. Type 2 diabetes was present in 414 participants (70.6%). The baseline mean (SD) estimated glomerular filtration rate was 51.9 (17.7) mL/min/1.73 m2, and median (interquartile range) UACR was 426.3 mg/g (205.3-888.5).
This study will inform dose selection for further clinical development and determine whether BI 690517, with or without background empagliflozin, has a favorable safety profile and potential for additive kidney protection in participants with CKD already treated with a renin-angiotensin system inhibitor.
醛固酮合酶（AS）抑制剂可能克服肾素-血管紧张素系统抑制后醛固酮产生增加。BI 690517 是一种正在研究用于慢性肾脏病（CKD）的 AS 抑制剂。
这项多中心、双盲、二期研究（NCT05182840）调查了每日口服 BI 690517 联合或不联合恩格列净 10mg 在 CKD 患者中的疗效和安全性。主要终点是治疗 14 周时与基线相比尿白蛋白与肌酐比值（UACR）的变化。2022 年 2 月 18 日至 2022 年 12 月 30 日，714 名已接受血管紧张素转换酶抑制剂（30.5%）或血管紧张素受体阻滞剂（69.8%）治疗的成年人被随机分为 8 周的导入期，以分配背景恩格列净（n=356）或安慰剂（n=358）。每组参与者随后被随机分为 BI 690517（3mg、10mg 或 20mg）或安慰剂的 14 周治疗期（1:1:1:1）。在进入导入期的 714 名参与者中，有 586 名被随机分配到治疗期。他们主要是男性（66.6%），白人（58.4%），平均（标准差[SD]）年龄为 63.8（11.3）岁。414 名参与者（70.6%）患有 2 型糖尿病。基线平均（SD）估计肾小球滤过率为 51.9（17.7）mL/min/1.73m2，中位数（四分位距）UACR 为 426.3mg/g（205.3-888.5）。
这项研究将为进一步的临床开发提供剂量选择，并确定 BI 690517 是否具有良好的安全性，以及是否在已经接受肾素-血管紧张素系统抑制剂治疗的 CKD 患者中具有潜在的额外肾脏保护作用。
