更新于：2024-12-12
Avenciguat
更新于：2024-12-12
概要
基本信息
非在研机构- |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)临床2期 |
特殊审评孤儿药 (欧盟)、孤儿药 (美国) |
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结构
分子式C34H38N4O5 |
InChIKeyKWNFFNFBUMFTHK-UHFFFAOYSA-N |
CAS号1579514-06-9 |
关联
22
项与 Avenciguat 相关的临床试验Pharmacokinetics, Safety, and Tolerability of BI 685509 in Subjects With Severe Liver Impairment (Child-Pugh Classification C) as Compared to Healthy Subjects
在发生首次失代偿事件后病情稳定（CTP5-7）的失代偿期肝硬化伴临床显著性门静脉高压（CSPH）的患者中评估口服BI685509一种剂量（上调至固定剂量方案）治疗门静脉高压8周后临床疗效的随机、双盲、安慰剂对照、平行组试验。
Relative Bioavailability of Two Different Tablet Formulations of BI 685509 and Investigation of the Effects of Food and Esomeprazole on the Pharmacokinetics of BI 685509 Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Four-way Crossover Trial)
100 项与 Avenciguat 相关的临床结果
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100 项与 Avenciguat 相关的转化医学
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100 项与 Avenciguat 相关的专利（医药）
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10
项与 Avenciguat 相关的文献（医药）2024-10-01LIVER TRANSPLANTATION
Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test
Article
作者: McRae, Michael P. ; Gashaw, Isabella ; Everson, Gregory T. ; Schoelch, Corinna ; Ertle, Judith ; Helmke, Steve M. ; Lawitz, Eric J.
New methods for measuring hepatic improvement in clinical trials and the clinic are needed. One new method, HepQuant SHUNT, detected dose-dependent improvements in hepatic function and portal physiology in the phase 1b study (NCT03842761) of avenciguat, an activator of soluble guanylyl cyclase that is being developed for the treatment of portal hypertension. Herein, we examined whether HepQuant Duo, an easy-to-administer test version, could similarly detect the effects of avenciguat. Twenty-three patients with Child-Pugh A cirrhosis and liver stiffness >15 kPa received either a placebo (n = 5) or a maximum twice-daily avenciguat dose of 1, 2, or 3 mg (n = 6 per group) for 28 days. The DuO test was performed at baseline and on days 11 and 27 in each subject. The test involved administering 40 mg of d4-cholate orally, measuring d4-cholate concentrations in serum at 20 and 60 minutes, and calculating portal hepatic filtration rate, disease severity index, portal-systemic shunting (SHUNT%), and hepatic reserve (HR%). Avenciguat demonstrated dose-dependent improvement in all test parameters. Changes from baseline in SHUNT% after 27 days’ treatment were 0.1 ± 9.0% for placebo, 1.7 ± 5.5% for 1 mg twice-daily, −3.2 ± 2.7% for 2 mg twice-daily, and −6.1 ± 5.0% for 3 mg twice-daily (paired t test for change from baseline p = 0.98, 0.48, 0.04, and 0.03, respectively). The changes detected by HepQuant DuO were similar to those previously observed and reported for HepQuant SHUNT. The results support further study of avenciguat in treating portal hypertension and spotlight the utility of HepQuant DuO in the development of drug therapy for liver disease. HepQuant DuO facilitates the use of function testing to measure hepatic improvement in clinical trials and the clinic.
2024-10-01NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 685509, a soluble guanylyl cyclase activator, in healthy volunteers: Results from two randomized controlled trials
Article
作者: Seitz, Friedeborg ; Bauer, Verena ; Schulze, Friedrich ; Wong, Diane ; Giessmann, Thomas
Abstract:
This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 685509 after oral single rising doses (SRDs) or multiple rising doses (MRDs) in healthy volunteers. In the SRD trial (NCT02694354; February 29, 2016), within each of the three dose groups (DGs), six subjects received BI 685509 (1.0, 2.5, or 5.0 mg) and two received placebo (N = 24). In the MRD trial (NCT03116906; April 17, 2017), within each of the five DGs, nine subjects received BI 685509 (uptitrated to 1 mg once daily [qd; DG1], 2.5 mg twice daily [DG2], 5.0 mg qd [DG3]; 3.0 mg three times daily [tid; DG4] or 4.0 mg tid [DG5]) and three received placebo, for 14–17 days (N = 60). In the SRD trial, 7/24 subjects (29.2%) had ≥ 1 adverse event (AE), most frequently orthostatic dysregulation (n = 4). In the MRD trial, 26/45 subjects (57.8%) receiving BI 685509 had ≥ 1 AE, most frequently orthostatic dysregulation and fatigue (each n = 12). Tolerance development led to a marked decrease in orthostatic dysregulation events (DG3). BI 685509 was rapidly absorbed after oral administration, and exposure increased in a dose-proportional manner after single doses. Multiple dosing resulted in near–dose-proportional increase in exposure and limited accumulation. BI 685509 pharmacokinetics appeared linear with time; steady state occurred 3–5 days after each multiple-dosing period. Increased plasma cyclic guanosine monophosphate and decreased blood pressure followed by a compensatory increase in heart rate indicated target engagement. BI 685509 was generally well tolerated; orthostatic dysregulation may be appropriately countered by careful uptitration.
2024-09-01JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Effect of Avenciguat on Albuminuria in Patients with CKD
Article
作者: Górriz, Jose Luis ; Tang, Sydney C W ; Gafor, Abdul Halim Abdul ; Desch, Marc ; Heerspink, Hiddo J L ; Iliev, Hristo ; Sun, Zhichao ; Steubl, Dominik ; Pergola, Pablo E ; Nangaku, Masaomi ; Cherney, David
Key Points:
Despite new treatments for CKD, kidney failure risk remains high, particularly where albuminuria remains.We report a prespecified pooled analysis of two randomized controlled trials assessing a soluble guanylate cyclase activator for CKD.Avenciguat led to improvements in albuminuria in patients with CKD with/without type 2 diabetes mellitus, with acceptable safety.
Background:
Avenciguat is a novel, potent soluble guanylate cyclase activator in development for CKD. Two trials investigated avenciguat in diabetic (NCT04750577) and non-diabetic (NCT04736628) CKD.
Methods:
A prespecified pooled analysis of two randomized, double-blind, placebo-controlled trials of identical design. Adults with CKD (eGFR ≥20 and <90 ml/min per 1.73 m2, urine albumin–creatinine ratio [UACR] ≥200 and <3500 mg/g) were randomized to 20 weeks of placebo or avenciguat 1, 2, or 3 mg three times daily (TID), adjunctive to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The primary end point was change from baseline in UACR in 10-hour urine at week 20, analyzed per protocol. The secondary end point was UACR change from baseline in first morning void urine at week 20. Safety was monitored throughout.
Results:
Overall, 500 patients (mean age 62 years [SD 13]; mean eGFR 44 ml/min per 1.73 m2 [SD 18] and median 10-hour UACR 719 [interquartile range, 379–1285] mg/g) received placebo (n=122) or avenciguat 1 mg (n=125), 2 mg (n=126), or 3 mg (n=127) TID. All 243 patients in study one and 27 of 261 patients in study two had diabetes mellitus. Avenciguat 1, 2, and 3 mg TID reduced UACR in 10-hour and first morning void urine versus placebo throughout the treatment period. At week 20, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UACR in 10-hour urine with avenciguat 1, 2, and 3 mg TID were −15.5% (−26.4 to −3.0), −13.2% (−24.6 to −0.1), and −21.5% (−31.7 to −9.8), respectively, analyzed per protocol. Corresponding changes in first morning void urine were −19.4% (−30.0 to −7.3), −15.5% (−26.9 to −2.5), and −23.4% (−33.5 to −11.8), respectively. Avenciguat was well tolerated; the overall frequency of adverse events was low and similar to placebo. The number of patients who discontinued the study drug because of adverse events with avenciguat 1, 2, and 3 mg TID were five (4%), 11 (9%), and 11 (9%), respectively, compared with four (3%) in the placebo group.
Conclusions:
Avenciguat lowered albuminuria and was well tolerated in patients with CKD.
Clinical Trial registry name and registration number::
A Study to Test the Effect of Different Doses of BI 685509 on Kidney Function in People With Diabetic Kidney Disease, NCT04750577, and A Study to Test the Effect of Different Doses of Avenciguat (BI 685509) on Kidney Function in People With Chronic Kidney Disease, NCT04736628.
Podcast:
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2024_06_27_ASN0000000000000418.mp3
100 项与 Avenciguat 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 肝硬化 | 临床2期 | 澳大利亚 | 2024-02-27 | |
| 肝硬化 | 临床2期 | 澳大利亚 | 2024-02-27 | |
| 系统性硬皮病 | 临床2期 | 美国 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 美国 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 日本 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 日本 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 阿根廷 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 阿根廷 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 澳大利亚 | 2022-12-14 | |
| 系统性硬皮病 | 临床2期 | 澳大利亚 | 2022-12-14 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 261 | (Avenciguat 1 mg TID) | 選選壓願範鬱顧窪積齋(窪夢積鑰淵願鬱夢廠遞) = 蓋築壓夢餘鏇齋築膚簾 築選獵膚糧鏇網願願壓 (蓋網衊製遞壓鬱鬱繭獵, 積願窪顧選構衊積襯鏇 ~ 膚醖蓋膚願衊艱糧鏇鹽) 更多 | - | 2024-09-04 | ||
(Avenciguat 2 mg TID) | 選選壓願範鬱顧窪積齋(窪夢積鑰淵願鬱夢廠遞) = 淵築顧夢襯顧淵鹽願鏇 築選獵膚糧鏇網願願壓 (蓋網衊製遞壓鬱鬱繭獵, 廠鬱膚鏇繭窪獵積夢願 ~ 選鹹簾簾構鑰鹽製觸艱) 更多 | ||||||
临床2期 | 243 | (BI 685509 1 mg TID) | 糧繭鏇餘齋網蓋糧廠襯(憲夢簾範簾壓簾繭繭憲) = 獵獵製鹽鹹鹹壓鑰鹽鹹 鬱廠顧糧窪鬱選鑰蓋壓 (襯鏇鹹範淵顧積觸選選, 範製簾窪衊淵鹽構鏇顧 ~ 膚網鹽選壓鑰鹹網壓窪) 更多 | - | 2024-07-23 | ||
(BI 685509 3 mg TID) | 糧繭鏇餘齋網蓋糧廠襯(憲夢簾範簾壓簾繭繭憲) = 齋製鑰鏇觸願衊蓋壓製 鬱廠顧糧窪鬱選鑰蓋壓 (襯鏇鹹範淵顧積觸選選, 蓋鑰鬱遞廠廠範鑰願獵 ~ 選窪糧鏇鏇膚網齋積憲) 更多 | ||||||
临床2期 | 500 | Avenciguat 1 mg TID | 鹽壓餘鬱獵製繭鏇醖顧(鑰餘醖膚蓋鹹鹹範壓鏇) = 餘鏇醖觸憲窪構廠願網 築憲簾醖淵鹹鏇網範築 (膚襯膚醖憲簾鏇網積獵, -26.4 ~ -3.0) 更多 | 积极 | 2024-05-25 | ||
Avenciguat 2 mg TID | 鹽壓餘鬱獵製繭鏇醖顧(鑰餘醖膚蓋鹹鹹範壓鏇) = 鹽鑰鬱壓淵觸廠齋蓋網 築憲簾醖淵鹹鏇網範築 (膚襯膚醖憲簾鏇網積獵, -24.6 ~ -0.1) 更多 | ||||||
临床2期 | 50 | BI-685509 30 mpk/day | 觸醖鏇製顧鏇膚觸鬱簾(齋糧夢壓獵夢襯簾憲鏇) = 壓蓋衊齋鏇簾餘蓋選襯 鑰壓築鏇鹽獵鬱淵觸範 (膚鹹膚觸糧製鹹壓窪簾 ) 更多 | 积极 | 2022-11-05 | ||
BI-685509 100 mpk/day | 觸醖鏇製顧鏇膚觸鬱簾(齋糧夢壓獵夢襯簾憲鏇) = 鹽窪願齋鹹鹹淵範憲簾 鑰壓築鏇鹽獵鬱淵觸範 (膚鹹膚觸糧製鹹壓窪簾 ) 更多 |
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