Neladenoson bialanate hydrochloride(Neladenoson bialanate hydrochloride)

概要

基本信息

药物类型

小分子化药

别名

Neladenoson bialanate

+ [1]

靶点

A1R

作用机制

A1R激动剂(腺苷A1受体激动剂)

治疗领域

心血管疾病

在研适应症-

非在研适应症

慢性心力衰竭慢性收缩性心力衰竭心脏衰竭

原研机构

Bayer AG

在研机构-

非在研机构

Bayer AG

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

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结构

分子式C35H34ClN7O4S2

InChIKeyWESNEIGKOAXSGX-VXKWHMMOSA-N

CAS号1239309-58-0

关联

10

项与 Neladenoson bialanate hydrochloride 相关的临床试验

NCT04320771 / Terminated临床1期

Investigation of Pharmacokinetics, Safety and Tolerability of Neladenoson Bialanate in Male and Female Subjects With Renal Impairment and in Age-, Gender-, and Weight-matched Healthy Subjects Following a Single Oral Dose of 10 mg Neladenoson Bialanate Given as IR Tablet in a Single-center, Nonrandomized, Non-controlled, Non-blinded, Study With Group Stratification

Neladenoson bialanate is currently under clinical development for a condition in which the heart has trouble pumping blood through the body (chronic heart failure). Renal impairment which co-occurs in patients with heart failure is a common condition in which the kidneys are not filtering the blood as well as they should. The goal of the study is to learn more about the safety of neladenoson bialanate, how it is tolerated and the way the body absorbs, distributes and excretes the study dug given as a single oral dose of 10 mg immediate release tablet in participants with renal impairment and healthy participants matched for age-, gender-, and weight

开始日期2017-11-02

申办/合作机构

Bayer AG

NCT04322253 / Terminated临床1期

Investigation of the Pharmacokinetics, Safety, and Tolerability of Neladenoson Bialanate in Subjects With Hepatic Impairment (Classified as Child Pugh A and B) and in Age-, Weight-, and Gender-matched Healthy Subjects, Following a Single Oral Dose in a Single-center, Non-randomized, Non-controlled, Non-blinded Study

Neladenoson bialanate is currently under clinical development for a condition in which the heart has trouble pumping blood through the body (chronic heart failure). Liver impairment is a condition in which the liver is not working as well as they should. The goal of the study is to learn more about the safety of neladenoson bialanate, how it is tolerated and the way the body absorbs, distributes and excretes the study dug given as a single oral dose neladenoson bialanate in participants with liver impairment and healthy participants matched for age-, gender-, and weight

开始日期2017-08-24

申办/合作机构

Bayer AG

NL-OMON44620 / CompletedN/A

Single center, open label, non-randomized, non-placebo controlled study to investigate the pharmacokinetics, metabolic disposition, and mass balance after single administration of 20 mg [14C]neladenoson bialanate (oral solution) in healthy male subjects. - Neladenoson bialanate mass balance study.

开始日期2017-06-06

申办/合作机构

Bayer AG

100 项与 Neladenoson bialanate hydrochloride 相关的临床结果

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100 项与 Neladenoson bialanate hydrochloride 相关的转化医学

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100 项与 Neladenoson bialanate hydrochloride 相关的专利（医药）

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9

项与 Neladenoson bialanate hydrochloride 相关的文献（医药）

2020-10-01·American Journal of Physiology-Heart and Circulatory Physiology2区 · 医学

More purinergic receptors deserve attention as therapeutic targets for the treatment of cardiovascular disease

2区 · 医学

Review

作者: Zhou (周稚超), Zhichao ; Wernly, Bernhard

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension, and diabetes. PRs have been targeted for the treatment of several cardiovascular diseases in a clinical setting. The P2Y12R antagonists such as clopidogrel, ticagrelor, and others are the most successful class of purinergic drugs targeting platelets for the treatment of acute coronary syndrome. In addition to targeting platelets, ticagrelor may exert P2Y12R-independent effect by targeting erythrocyte-mediated purinergic activation. The partial A1R agonist neladenoson and the A2AR agonist regadenoson have been applied in cardiovascular medicine. In experimental studies, many other PRs have been shown to play a significant role in the development and progression of cardiovascular diseases, and targeting these receptors have resulted in promising outcomes. Therefore, many of these PRs including A2BR, A3R, P2X3R, P2X4R, P2X7R, P2Y1R, P2Y4R, P2Y6R, and P2Y11R can be considered as therapeutic targets. However, the multitude of PR subtypes expressed in different cells of the cardiovascular system may constitute a challenge whether single or multiple receptors should be targeted at the same time for the best efficacy. The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development.

2019-11-01·European Journal of Heart Failure

Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: a phase IIb, randomized, double‐blind, placebo‐controlled trial

Article

作者: Senni, Michele ; Pap, Akos F. ; Bax, Jeroen J. ; Butler, Javed ; Ferreira, Anna C. ; Voors, Adriaan A. ; van der Laan, Michael ; Hernandez, Adrian F. ; Wirtz, Antonieta B.

AbstractAimsNeladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose–response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF).Methods and resultsPANTHEON was a dose‐finding, phase IIb, randomized, double‐blind, placebo‐controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT‐proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose–effect of neladenoson bialanate on changes in NT‐proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high‐sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose‐dependent increase in creatinine and cystatin C, and a dose‐dependent decrease in estimated glomerular filtration rate and heart rate.ConclusionsIn patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose‐dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose‐dependent decrease in renal function.Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02992288.

2019-06-04·JAMA1区 · 医学

A Randomized Clinical Trial

1区 · 医学

Article

作者: Kitzman, Dalane W. ; Shah, Sanjiv J. ; Bomfim Wirtz, Antonieta ; Voors, Adriaan A. ; Pap, Akos Ferenc ; McMurray, John J. V. ; Viethen, Thomas ; Huang, Erya ; Solomon, Scott D.

ImportanceHeart failure with preserved ejection fraction (HFpEF) lacks effective treatments. Based on preclinical studies, neladenoson bialanate, a first-in-class partial adenosine A1 receptor agonist, has the potential to improve several heart failure-related cardiac and noncardiac abnormalities but has not been evaluated to treat HFpEF.ObjectivesTo determine whether neladenoson improves exercise capacity, physical activity, cardiac biomarkers, and quality of life in patients with HFpEF and to find the optimal dose.Design, Setting, and ParticipantsPhase 2b randomized clinical trial conducted at 76 centers in the United States, Europe, and Japan. Patients (N = 305) with New York Heart Association class II or III HFpEF with elevated natriuretic peptide levels were enrolled between May 10, 2017, and December 7, 2017 (date of final follow-up: June 20, 2018).InterventionsParticipants were randomized (1:2:2:2:2:3) to neladenoson (n = 27 [5 mg], n = 50 [10 mg], n = 51 [20 mg], n = 50 [30 mg], and n = 51 [40 mg]) or matching placebo (n = 76) for 20 weeks of treatment.Main Outcomes and MeasuresThe primary end point was change in 6-minute walk test distance from baseline to 20 weeks (minimal clinically important difference, 40 m). Key safety measures included bradyarrhythmias and adverse events. To evaluate the effects of varying doses of neladenoson, a multiple comparison procedure with 5 modeling techniques (linear, Emax, 2 variations of sigmoidal Emax, and quadratic) was used to evaluate diverse dose-response profiles.ResultsAmong 305 patients who were randomized (mean age, 74 years; 160 [53%] women; mean 6-minute walk test distance, 321.5 m), 261 (86%) completed the trial and were included in the primary analysis. After 20 weeks of treatment, the mean absolute changes from baseline in 6-minute walk test distance were 0.2 m (95% CI, -12.1 to 12.4 m) for the placebo group; 19.4 m (95% CI, -10.8 to 49.7 m) for the 5 mg of neladenoson group; 29.4 m (95% CI, 3.0 to 55.8 m) for 10 mg of neladenoson group; 13.8 m (95% CI, -2.3 to 29.8 m) for 20 mg of neladenoson group; 16.3 m (95% CI, -1.1 to 33.6 m) for 30 mg of neladenoson group; and 13.0 m (95% CI, -5.9 to 31.9 m) for 40 mg of neladenoson group. Because none of the neladenoson groups achieved the clinically relevant 40-m increase in 6-minute walk test distance from baseline, an optimal dose of neladenoson was not identified. There was no significant dose-response relationship for the change in 6-minute walk test distance among the 5 different dose-response models (P = .05 for Emax; P = .18 for quadratic; P = .21 for sigmoidal Emax 1; P = .39 for linear; and P = .52 for sigmoidal Emax 2). Serious adverse events were similar among the neladenoson groups (61/229 [26.6%]) and the placebo group (21/76 [27.6%]).Conclusions and RelevanceAmong patients with HFpEF, there was no significant dose-response relationship detected for neladenoson with regard to the change in exercise capacity from baseline to 20 weeks. In light of these findings, novel approaches will be needed if further development of neladenoson for the treatment of patients with HFpEF is pursued.Trial RegistrationClinicalTrials.gov Identifier: NCT03098979.

100 项与 Neladenoson bialanate hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB13138

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
心脏衰竭	临床2期	中国	Bayer AG	2018-06-13
慢性收缩性心力衰竭	临床2期	荷兰	Bayer AG	2014-01-28
慢性收缩性心力衰竭	临床2期	德国	Bayer AG	2014-01-28
慢性收缩性心力衰竭	临床2期	意大利	Bayer AG	2014-01-28
慢性收缩性心力衰竭	临床2期	波兰	Bayer AG	2014-01-28
慢性心力衰竭	临床2期	荷兰	Bayer AG	2013-11-29

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临床结果

适应症

分期

评价

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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


NCT02992288 (PANTHEON, Pubmed) 人工标引	临床2期	慢性心力衰竭	427	neladenoson bialanate	(壓積獵範壓鑰淵鑰糧醖): P-Value = 0.74 更多	不佳	2019-11-01
				Placebo
NCT03098979 (PANACHE, CTgov)	临床2期	慢性心力衰竭	305	Placebo	鹽構鑰廠遞鑰積夢鬱鹹(壓鏇淵顧膚憲糧壓遞廠) = 壓範製構襯鹹範糧構顧遞壓選鏇鹹構蓋廠遞廠 (夢鬱製遞遞簾繭鬱築築, 壓醖餘鏇壓觸鏇鑰鏇夢 ~ 網窪餘範糧襯壓鑰範廠) 更多	-	2019-07-23
NCT03098979 (Pubmed \| J Coll Physicians Surg Pak)	临床2期	射血分数保留型心力衰竭	305	Neladenoson 5 mg	遞襯壓範醖鑰構鑰繭鹹(鏇艱衊製膚簾壓憲廠淵) = 夢夢艱網蓋顧壓鏇鑰範繭襯積蓋積醖構獵蓋鹽 (願鏇鬱範憲積膚製構製, -10.8 ~ 49.7)	-	2019-06-04
				Neladenoson 10 mg	遞襯壓範醖鑰構鑰繭鹹(鏇艱衊製膚簾壓憲廠淵) = 廠鏇衊獵繭觸獵鑰願簾繭襯積蓋積醖構獵蓋鹽 (願鏇鬱範憲積膚製構製, 3.0 ~ 55.8)
NCT02992288 (PANTHEON, CTgov)	临床2期	慢性心力衰竭	427	Placebo	醖淵憲夢顧網餘願醖選(網鹽顧繭鑰築壓醖構積) = 鬱窪齋蓋壓築艱窪膚鬱鹽蓋廠鹽繭鑰簾壓網糧 (積繭簾蓋製鹹網壓鬱鹹, 遞繭繭獵衊積鹽餘蓋齋 ~ 築範壓齋廠製觸積艱鹹) 更多	-	2019-04-23