更新于：2024-09-07
Avenciguat
更新于：2024-09-07
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 (美国) |
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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5
项与 Avenciguat 相关的文献（医药）Hepatology communications
Safety and pharmacokinetics of BI 685509, a soluble guanylyl cyclase activator, in patients with cirrhosis: A randomized Phase Ib study
Article
作者: Reiberger, Thomas ; Wong, Diane ; Schoelch, Corinna ; Coxson, Harvey O. ; Ertle, Judith ; Lawitz, Eric J. ; Schattenberg, Jörn M.
Background::
Portal hypertension is a severe complication of cirrhosis. This Phase Ib study (NCT03842761) assessed the safety, tolerability, and pharmacokinetics of soluble guanylyl cyclase activator BI 685509 in patients with mild or moderate hepatic impairment (Child–Pugh [CP] A or B cirrhosis) and healthy volunteers (HVs).
Methods::
In this single-center, randomized, placebo-controlled study, patients received BI 685509 (maximum doses: 1, 2, or 3 mg, twice daily [BID]) or placebo for 28 days. HVs received one 0.5 mg dose of BI 685509 or placebo.
Results::
In total, 64 participants (CP-A, n=24; CP-B, n=25; HVs, n=15) were included; most commonly with NAFLD (36.7%), alcohol-associated (30.6%), or chronic viral hepatitis-related cirrhosis (28.6%). In patients with CP-A cirrhosis, drug-related adverse events (AEs) occurred in 5.6% of BI 685509-treated patients and 16.7% of placebo recipients. In patients with CP-B cirrhosis, drug-related AEs occurred in 26.3% of BI 685509-treated patients only. No serious AEs occurred in patients with CP-A cirrhosis; in patients with CP-B cirrhosis, serious AEs (not drug-related) occurred in 10.5% of BI 685509-treated patients and 16.7% of patients receiving placebo. BI 685509 was rapidly absorbed; exposure increased with dosage and was similar between etiologies and between patients with CP-A cirrhosis and patients with CP-A cirrhosis but lower in HVs. The mean percentage portal–systemic shunt fraction was measured in patients with CP-A cirrhosis and decreased at the end of treatment in the 2 mg BID (–11.2 ± 11.9%) and 3 mg BID (–14.0 ± 8.4%) BI 685509 dose groups, but not in the placebo group (+1.0 ± 27.3%).
Conclusion::
BI 685509 was generally well tolerated, with 3 serious, not drug-related AEs reported in patients with CP-B cirrhosis. In patients with CP-A cirrhosis, portal–systemic shunt fraction in the exploratory efficacy analysis was reduced by 2 mg BID and 3 mg BID BI 685509.
2023-08-01Diabetes, obesity & metabolism
Safety, tolerability, pharmacodynamics and pharmacokinetics of the soluble guanylyl cyclase activator BI 685509 in patients with diabetic kidney disease: A randomized trial.
Article
作者: Wenz, Arne ; Nangaku, Masaomi ; Desch, Marc ; de Zeeuw, Dick ; Heerspink, Hiddo J L ; Cherney, David Z I ; Schulze, Friedrich ; Cardona, Jose
AIMS:
Albuminuria is associated with abnormalities in the nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate pathway. We assessed safety and efficacy of the NO-independent sGC activator BI 685509 in patients with diabetic kidney disease and albuminuria.
MATERIALS AND METHODS:
In this Phase Ib trial (NCT03165227), we randomized patients with type 1 or 2 diabetes, estimated glomerular filtration rate (eGFR) 20-75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200-3500 mg/g to oral BI 685509 (1 mg three times daily, n = 20; 3 mg once daily, n = 19; 3 mg three times daily, n = 20, after final titration) or placebo (n = 15) for 28 days. Changes from baseline in UACR in first morning void (UACRFMV ) and 10-hour (UACR10h ) urine (3 mg once daily/three times daily only) were assessed.
RESULTS:
Baseline median eGFR and UACR were 47.0 mL/min/1.73 m2 and 641.5 mg/g, respectively. Twelve patients had drug-related adverse events (AEs; 16.2%: BI 685509, n = 9; placebo, n = 3), most frequently hypotension (4.1%: BI 685509, n = 2; placebo, n = 1) and diarrhoea (2.7%: BI 685509, n = 2; placebo, n = 0). Four patients experienced AEs leading to study discontinuation (5.4%: BI 685509, n = 3; placebo, n = 1). Placebo-corrected mean UACRFMV decreased from baseline in the 3-mg once-daily (28.8%, P = 0.23) and three-times-daily groups (10.2%, P = 0.71) and increased in the 1-mg three-times-daily group (6.6%, P = 0.82); changes were not significant. UACR10h decreased by 35.3% (3 mg once daily, P = 0.34) and 56.7% (3 mg three times daily, P = 0.09); ≥50.0% of patients (UACR10h 3 mg once daily/three times daily) responded (≥20% UACR decrease from baseline).
CONCLUSIONS:
BI 685509 was generally well tolerated. Effects on UACR lowering merit further investigation.
2023-07-01The Journal of pharmacology and experimental therapeutics
Soluble Guanylyl Cyclase Activator BI 685509 Reduces Portal Hypertension and Portosystemic Shunting in a Rat Thioacetamide-Induced Cirrhosis Model.
Article
作者: Qian, Hu Sheng ; Jones, Amanda K ; Wilks, James ; Ng, Khing Jow ; Brilisauer, Klaus ; Villalona, Jorge ; Zeveleva, Svetlana ; McHugh, Mark ; Bretschneider, Tom ; Fryer, Ryan M ; Chen, Hongxing
Portal hypertension (PT) commonly occurs in cirrhosis. Nitric oxide (NO) imbalance contributes to PT via reduced soluble guanylyl cyclase (sGC) activation and cGMP production, resulting in vasoconstriction, endothelial cell dysfunction, and fibrosis. We assessed the effects of BI 685509, an NO-independent sGC activator, on fibrosis and extrahepatic complications in a thioacetamide (TAA)-induced cirrhosis and PT model. Male Sprague-Dawley rats received TAA twice-weekly for 15 weeks (300-150 mg/kg i.p.). BI 685509 was administered daily for the last 12 weeks (0.3, 1, and 3 mg/kg p.o.; n = 8-11 per group) or the final week only (Acute, 3 mg/kg p.o.; n = 6). Rats were anesthetized to measure portal venous pressure. Pharmacokinetics and hepatic cGMP (target engagement) were measured by mass spectrometry. Hepatic Sirius Red morphometry (SRM) and alpha-smooth muscle actin (αSMA) were measured by immunohistochemistry; portosystemic shunting was measured using colored microspheres. BI 685509 dose-dependently increased hepatic cGMP at 1 and 3 mg/kg (3.92 ± 0.34 and 5.14 ± 0.44 versus 2.50 ± 0.19 nM in TAA alone; P < 0.05). TAA increased hepatic SRM, αSMA, PT, and portosystemic shunting. Compared with TAA, 3 mg/kg BI 685509 reduced SRM by 38%, αSMA area by 55%, portal venous pressure by 26%, and portosystemic shunting by 10% (P < 0.05). Acute BI 685509 reduced SRM and PT by 45% and 21%, respectively (P < 0.05). BI 685509 improved hepatic and extrahepatic cirrhosis pathophysiology in TAA-induced cirrhosis. These data support the clinical investigation of BI 685509 for PT in patients with cirrhosis. SIGNIFICANCE STATEMENT: BI 685509 is an NO-independent sGC activator that was tested in a preclinical rat model of TAA-induced nodular, liver fibrosis, portal hypertension, and portal systemic shunting. BI 685509 reduced liver fibrosis, portal hypertension, and portal-systemic shunting in a dose-dependent manner, supporting its clinical assessment to treat portal hypertension in patients with cirrhosis.
2
项与 Avenciguat 相关的新闻（医药）2024-07-08
·药融圈
临床3期抗体药物偶联物临床2期临床失败申请上市
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 | 美国 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 中国 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 日本 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 奥地利 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 加拿大 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 法国 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 德国 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 罗马尼亚 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 韩国 | 2024-01-03 | |
| 肝硬化 | 临床2期 | 西班牙 | 2024-01-03 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 261 | (Avenciguat 1 mg TID) | 憲繭廠遞網糧鬱簾選鏇(鬱獵齋範網選遞壓願糧) = 憲選鏇淵淵糧夢簾製鹹 願積醖遞淵範遞衊廠構 (繭網遞夢製構願窪窪憲, 衊夢鬱顧齋艱蓋膚築獵 ~ 鏇淵膚遞壓蓋醖遞鬱構) 更多 | - | 2024-09-04 | ||
(Avenciguat 2 mg TID) | 憲繭廠遞網糧鬱簾選鏇(鬱獵齋範網選遞壓願糧) = 醖鏇築顧積繭鹹襯獵淵 願積醖遞淵範遞衊廠構 (繭網遞夢製構願窪窪憲, 網衊膚構顧鬱繭遞餘顧 ~ 蓋鹽廠製繭顧選製艱膚) 更多 | ||||||
临床2期 | 243 | (BI 685509 1 mg TID) | 鏇艱顧製積願糧積遞構(獵糧顧網築醖憲網製願) = 淵築鏇網範構構積觸繭 餘齋獵廠範憲獵顧範顧 (膚襯蓋選繭襯膚獵淵夢, 積窪遞獵繭夢膚鬱鑰壓 ~ 餘製遞鏇膚顧窪築衊繭) 更多 | - | 2024-07-23 | ||
(BI 685509 3 mg TID) | 鏇艱顧製積願糧積遞構(獵糧顧網築醖憲網製願) = 廠餘構壓蓋窪齋鏇繭獵 餘齋獵廠範憲獵顧範顧 (膚襯蓋選繭襯膚獵淵夢, 鏇願壓艱醖夢鏇願醖簾 ~ 餘壓夢積憲繭襯衊鏇製) 更多 | ||||||
临床2期 | 500 | Avenciguat 1 mg TID | 廠獵鏇醖艱製蓋構鹹獵(選膚窪鑰構糧壓簾鹹鹽) = 鏇鹽齋衊範蓋衊衊衊廠 積憲鬱淵顧淵餘窪糧選 (齋鬱衊膚願繭構鹽廠獵, -26.4 ~ -3.0) 更多 | 积极 | 2024-05-25 | ||
Avenciguat 2 mg TID | 廠獵鏇醖艱製蓋構鹹獵(選膚窪鑰構糧壓簾鹹鹽) = 憲遞膚構淵衊範糧醖繭 積憲鬱淵顧淵餘窪糧選 (齋鬱衊膚願繭構鹽廠獵, -24.6 ~ -0.1) 更多 | ||||||
临床2期 | 50 | BI-685509 30 mpk/day | 衊廠鏇膚夢簾選鏇襯鹽(鏇鑰糧觸網醖壓窪鏇構) = 鹹衊廠齋鹽願襯範鹹鹹 衊膚獵壓鬱壓獵衊衊觸 (構顧願鏇範遞顧憲觸衊 ) 更多 | 积极 | 2022-11-05 | ||
BI-685509 100 mpk/day | 衊廠鏇膚夢簾選鏇襯鹽(鏇鑰糧觸網醖壓窪鏇構) = 鏇顧觸鬱網窪襯醖夢廠 衊膚獵壓鬱壓獵衊衊觸 (構顧願鏇範遞顧憲觸衊 ) 更多 |
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