更新于：2024-05-12

Vorapaxar Sulfate

硫酸沃拉帕沙

更新于：2024-05-12

概要

概要

基本信息

药物类型

小分子化药

别名

Carbamic acid, [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(1E)-2-[5-(3-fluorophenyl)-2- pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]-, ethyl ester、Carbamic acid, N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-9-[(E)-2-[5-(3-fluorophenyl)-2-pyridinyl]ethenyl]dodecahydro-1-methyl-3-oxonaphtho[2,3-c]furan-6-yl]-, ethyl ester、Ethyl N-[(3R,3aS,4S,4aR,7R,8aR,9aR)-4-[(E)-2-[5-(3-fluorophenyl)-2-pyridyl]vinyl]-3-methyl-1-oxo-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-3H-benzo[f]isobenzofuran-7-yl]carbamate

+ [7]

靶点

PAR-1

作用机制

F2R拮抗剂(蛋白酶活化受体1拮抗剂)

治疗领域

神经系统疾病心血管疾病

在研适应症

动脉血栓形成冠状动脉疾病心肌梗塞+ [3]

非在研适应症

急性冠状动脉综合征凝血障碍大脑梗塞+ [3]

原研机构

Merck Sharp & Dohme Corp.

在研机构

Xspire Pharma LLC

Key Therapeutics, LLC初创企业

非在研机构

Merck GmbH

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLC

最高研发阶段批准上市

首次获批日期

美国 (2014-05-08),

冠状动脉疾病心肌梗塞外周动脉疾病+ [2]

最高研发阶段(中国)无进展

特殊审评快速通道 (美国)、临床急需境外新药 (中国)

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结构

分子式C29H35FN2O8S

InChIKeyNQRYCIGCIAWEIC-CKLVGUEFSA-N

CAS号705260-08-8

关联

项与硫酸沃拉帕沙相关的临床试验

NCT04677023 / Unknown statusN/AIIT

Clinical Evaluation of Organically Modified Ceramic Resin Composite Versus Conventional Bulkfill Resin Composite in Proximal Compound Posterior Restorations: Randomized Clinical

In patients with compound posterior proximal cavities, will the use of organically modified ceramic resin composite restorative material have similar clinical performance to conventional bulk fill resin composite, evaluation of restorations will be done at baseline,six and twelve months using World Dental Federation FDI criteria.

开始日期2021-01-01

申办/合作机构

Cairo University

NCT02975583 / Withdrawn临床4期IIT

A Double-blind, Randomized, Parallel Design Two Center Study to Compare the Effect of Vorapaxar vs. Placebo on Lower Extremity Vein Graft Maturation, Remodeling, and Function

There are no medical therapies indicated for reduction of limb ischemic events. Studies of dual-antiplatelet therapy with aspirin and clopidogrel versus aspirin alone (CASPAR) as well as studies of systemic anticoagulation (WAVE) have shown no benefit for either strategy in the reduction in limb vascular events. Surgical bypass grafting involves harvesting of the vein, warm ischemia with disruption of vaso vasorum, ischemia-reperfusion, and finally heightened hemodynamic stress in the new arterial environment. Vein grafts rapidly remodel in response to the increase in blood flow and pressure in an attempt to normalize them into physiological range. The investigators have previously identified 3 distinct temporal phases of the remodeling process: During the first 30 days following implantation is a critical period of luminal enlargement which appears to be an endothelium-independent process. The second phase occurs between 1 and 3 months and represents a period of stiffening of the vein graft indicating synthesis of fibrous proteins. The third period is referred to as biochemical remodeling wherein the vein recovers clinically measureable endothelial function. It is likely diabetes mellitus impacts each of these phases. TRA2°P-TIMI 50 demonstrated a reduction in acute limb ischemic (ALI) events (42% reduction) and urgent peripheral arterial revascularizations (35% reduction), a finding unique among medical therapies. While the temporal trend in reduction in ALI events occurred early and late after exposure suggestion an antithrombotic mechanism, the reduction in elective revascularization occurred later suggested beneficial effects beyond platelet inhibition. The purpose of this trial is to study the physiological impact of vorapaxar on lower extremity bypass graft maturation and function.

开始日期2017-10-01

申办/合作机构

Vanderbilt University

[+1]

NCT02660866 / Unknown status临床4期

Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)

This is a Phase 4, randomized clinical trial to evaluate whether addition of Vorapaxar 2.08 mg daily vs. placebo daily on background antiplatelet therapy, prescribed for 6 months to patients with established peripheral artery disease (PAD) and Intermittent Claudication (IC) treated with standard medical therapy (SMT) would lead to an improvement in the peak walking time (PWT).

开始日期2016-07-01

申办/合作机构

Northwest Texas Healthcare System, Inc.

100 项与硫酸沃拉帕沙相关的临床结果

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100 项与硫酸沃拉帕沙相关的转化医学

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100 项与硫酸沃拉帕沙相关的专利（医药）

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919

项与硫酸沃拉帕沙相关的文献（医药）

2024-02-01·British Journal of Clinical Pharmacology

Investigation of the absolute bioavailability, mass balance, metabolism, and excretion of the cholesterol 24‐hydroxylase inhibitor soticlestat in healthy volunteers

Article

作者: Hui, Tom ; Stevenson, Annette ; Hunt, Allen ; Zhu, Sean Xiaochun ; Hsiao, Samuel ; Chen, Hao ; Han, Steve ; Ballard, T Eric ; Asgharnejad, Mahnaz ; Yin, Wei ; Chowdhury, Swapan K ; Li, Yuexian

Abstract:

Aims:

Our aim was to determine the absolute bioavailability, mass balance, metabolism and excretion of soticlestat (TAK‐935).

Methods:

An open‐label, two‐period, single‐site, phase 1 study was conducted in six healthy men. In Period 1, a single 300 mg dose of soticlestat was administered orally, followed by a 15‐min intravenous infusion of [14C]soticlestat 50 μg (~1 μCi) 10 min later. In Period 2, a single 300 mg dose (~100 μCi) of [14C]soticlestat in solution was administered orally. Samples were collected, analysed for radioactivity or unchanged soticlestat, and profiled for metabolites.

Results:

In Period 1, soticlestat had an absolute bioavailability of 12.6% (90% confidence interval, 7.81–20.23%). In Period 2, there was near‐complete recovery of total radioactivity (TRA) following a 300 mg dose of [14C]soticlestat: urine, 94.8% (standard deviation [SD], 1.35%); faeces, 2.7% (SD, 1.67%). Of TRA, 0.1% (SD, 0.09%) and 0.6% (SD, 0.21%) were recovered as soticlestat and metabolite M‐I in urine, respectively. In plasma, soticlestat and M‐I reached geometric mean maximum observed concentrations of 1352 ng/mL (geometric percent coefficient of variation [gCV%], 61.3) and 253.2 ng/mL (gCV%, 44.1) after 25 min and declined with mean terminal half‐lives (SD) of 5.7 (2.90) and 2.0 (0.15) h, respectively. Soticlestat represented 4.9% of TRA in plasma. Soticlestat was rapidly eliminated primarily via O‐glucuronidation to metabolite M3, which was the dominant species in plasma (92.6%) and urine (86%).

Conclusions:

This study indicates that soticlestat and its metabolites are rapidly cleared and eliminated, lowering the risk of dose accumulation from repeated dosing and supporting further investigation of soticlestat.

2024-05-01·Journal of Thrombosis and Haemostasis

Quantifying the benefit-risk trade-off for individual patients in a clinical trial: principles and antithrombotic case study

Article

作者: Stone, Gregg W ; Pocock, Stuart J ; Ashby, Deborah ; Baumgartner, Richard ; Owen, Ruth ; Mt-Isa, Shahrul ; Gregson, John

BACKGROUND:

A treatment's overall favorable benefit-risk profile does not imply that every individual patient will benefit from the treatment.

OBJECTIVES:

To describe a statistical methodology for quantifying the benefit-risk trade-off in individual patients.

METHODS:

The method requires a large randomized controlled trial containing a primary efficacy outcome and a primary safety outcome, for instance, the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 placebo-controlled trial of vorapaxar in 17 779 patients following myocardial infarction. Multivariate regression models predict each individual patient's risk of ischemic events (benefit) and major bleeding events (harm) based on their profile. Hence, each patient's predicted benefit from vorapaxar (reduction in ischemic events) and predicted risk (increase in bleeding events) were estimated. The relative importance of ischemic and bleeding events based on links to all-cause mortality was quantified, although the limitations of such weightings are noted.

RESULTS:

Overall results demonstrated both clear benefit and harm from vorapaxar. Substantial interindividual variation in both benefit and risk facilitated distinguishing patients with a favorable benefit-risk trade-off from those who did not. Such findings were applied to recommend vorapaxar in as many as 98.3% of patients in which a favorable mortality-weighted benefit-risk trade-off was present, in 77.2% of patients with ischemic benefit 20% greater than bleeding risk, or in as few as 45.5% of patients if an annual decrease in ischemic risk of ≥0.5% was also required.

CONCLUSION:

While overall randomized controlled trials of treatment benefit vs risk are valuable, models determining each individual patient's estimated absolute benefit and risk provide more useful insight regarding patient-specific benefit-risk trade-offs to better enable personalized therapeutic decision-making.

2024-01-01·International Journal of Biological Macromolecules

Effective application of citric acid treated Trapa natans and Citrullus lanatus lignocellulosic macromolecules for adsorptive remediation of acid Violet-7 dye

Article

作者: Al-Abbad, Eman A ; Al-Thagafi, Zahrah T ; Alsantali, Reem I ; Hussain, Muhammad Sadiq ; Samin, Ghufrana ; Dar, Amara ; Jahangir, Muhammad Muzammil ; Rehman, Rabia ; Akram, Mehwish

The peels of Trapa natans (TRA) and Citrullus lanatus (CIT), were modified with a variety of chemicals to boost their surface for the optimization of adsorption performance by providing a greater number of additional active binding sites. Citric acid-processed peels (TRAC and CITC) had shown more favorable adsorption performance to eradicate acid violet 7 dye (AVS). Extra and additional active sites generated after chemical processing, including hydroxyl (OH), carboxyl (COOH), amines NH₂, carbonyl, and ester (-O-CO-) groups, as evidenced from FTIR and SEM characterizations, may boost the potential of physicochemical integration of adsorbent surface activity in order to promote and encourage the retention of hazardous and risky AVS molecules from the water. The Langmuir isotherm assessed the q_max for the adsorption of AVS on TRAC, CITC, TRA, and CIT to be 212.8, 294, 24.3, and 60.6 mg/g, respectively, whereas the correlation coefficients assessed for both TRAC and CITC were 0.98 and for TRA and CIT were 0.97, closer to unity reflecting monolayer physio-sorption. According to Temkin, the adsorption of AVS on TRAC, TRA, CITC, and CIT gives "B_T" values of 1.275, 0.947, 1.085, and 1.211 mg/g, also suggesting physio-sorption. Therefore, chemically modified peels can be employed for detoxification of AVS.

项与硫酸沃拉帕沙相关的新闻（医药）

2023-12-25

·动脉网

发力小分子抑制剂，这家企业开发PD-L1+化疗全口服联用新方案

2023年12月，广州再极医药科技有限公司（以下简称“再极医药”）宣布：再极医药与温州大学医学院联合开展的口服PD-L1药物MAX-10181治疗脑胶质瘤的动物药效数据，获准在2024年美国癌症协会年会（AACR）进行展示，实现了脑胶质瘤治疗的全球首创的口服肿瘤免疫检查点抑制剂与口服化疗药物的联合用药。 MAX-10181是再极医药数条“first-in-class”临床管线中的一条，于今年10月获NMPA批准进入临床II期。两个月前，再极医药在第八届中国医药创新与投资大会上首次报告了另一条“first-in-class”管线MAX-40279治疗急性髓系白血病（AML）的临床数据。令人振奋的是有复发难治的AML患者经过MAX-40279的治疗，获得重生。 MAX-40279已经在2018获得了美国FDA孤儿药的资质，并且在2019年获国家新药创制重大专项，目前在NMPA批准的临床II期试验中。创办于2016年的创新药企再极医药，已经完成多轮亿元级融资，投资方包括聚焦资本、龙磐资本、晨兴资本等。公司聚焦靶向疗法和免疫疗法，研发first-in-class/best-in-class的小分子药物，产品管线包括急髓性白血病（AML）、多种实体瘤及自身免疫性皮肤病等，囊括小分子药物口服、外用、核素三大应用方式。目前，再极医药共有6条公开管线，其中两条进入临床II期，三条进入临床I期。再极医药创始人王玉光博士再极医药创始人王玉光博士，自1978年开始于山东医科大学（现为山东大学医学院）攻读药学本科及硕士学位，后又于1986年到美国堪萨斯大学深造，攻读药物化学和药物设计的博士学位。毕业后，王玉光博士先后加入跨国制药公司（MNC）先灵葆雅和中国CRO公司睿智化学，积累了从跨国公司的科研、管理，商务合作到CRO公司的各项服务的丰富经验，他既在跨国制药公司（MNC）发明新药Vorapaxar，又在CRO公司成功助力4家公司实现NASDAQ上市。王玉光博士发表论文近30篇，拥有7项世界专利，12项美国专利。借着再极医药多个好消息传来的契机，动脉网有幸与王玉光博士对话，听他讲述深耕药物分子设计近30年来的故事和创办再极医药的始终。投身药物分子设计近30年，曾参与开发全球首个口服PAR-1小分子抑制剂1986年，受到将抗肿瘤药物卡铂产业化的导师王慧才教授的影响，王玉光怀揣着一颗学习先进技术、报效祖国的朴素想法，奔赴美国堪萨斯大学药学院，学习药物化学和药物设计。毕业后，王玉光博士受邀加入了跨国药企先灵葆雅，开启了长达19年的职业生涯。在先灵葆雅的前10年，王玉光博士主要担任研发科学家，负责推动创新项目进入临床试验，主要方向为中枢神经及心血管疾病。脑卒中、脑血栓是神经中枢疾病中非常棘手的难题，存在可用药物少且存在出血风险的痛点。上世纪末，多家MNC和创新药企投身于这一研究中，先灵葆雅也加入“战场”开发抗血栓而不抗凝血的新药——也就是后来获得FDA和EMA批准的全球首个口服PAR-1小分子抑制剂Vorapaxar——默沙东以411亿美元收购先灵葆雅的动因之一。1996年，当先灵葆雅前两代化合物设计都以毒性相关问题失败后，向全公司的科学家求助。“所有的科学家都绞尽脑汁，每个人都在尝试设计新的化合物。”王玉光博士笑谈到。作为一位极具冒险精神的科学家，王玉光博士也加入了第三代的化合物研发，设计研发出新的化合物，也就是Vorapaxar。由此，王玉光博士获得了1996年的先灵葆雅研发总裁奖以及2008年美国爱迪生发明专利奖。在先灵葆雅工作期间，王玉光博士总共拿了三次先灵葆雅研发总裁奖。2002年以后，因为在研发领域的出色表现，王玉光博士转而担任科研总监开启了全新的挑战。“在这个岗位主要负责项目BD和外包服务合作，从多个维度为公司降低医药研发的费用。”王玉光博士说。从2003年开始，由于工作原因，王玉光博士开始频繁往返于中美，与国内药企特别是医药CRO公司进行合作，包括药明康德、睿智化学/尚华医药集团等。2009年，先灵葆雅被默沙东收购前夕，受到国内CRO药企睿智化学邀请，王玉光博士加入睿智化学担任高级副总裁，每年参与管理50个以上的新药研发项目，成功助力4家药企在纳斯达克上市。加入睿智化学还不到两年，便成功推动其在美国纽交所上市。说起创业想法的萌发，王玉光博士坦言，“创业从来不是我主要的想法，对于我们这代人来说，做出新药是我们的使命，也是我们的历史任务。所以于我而言，因为国内很少有完全能实现我想法的平台或药企，难以给予我最大的自由度去创造，创业就变成我完成使命最直接的途径了。我不是为了创业而创业，我所有的想法都是为了研发创新药物，解决临床未满足的需求，研药救治，给生命以希望，是我给再极医药制定的目标。”2015年，被称为中国创新药历史上最重要的“44号文”出台，这份由国办印发的《国务院关于改革药品医疗器械审评审批制度的意见》令无数科学家振奋。政策、人才和市场等要素已经齐备的机遇下，得益于过去近30年的一线研发、科研项目管理的经验，王玉光博士随即在2016年创办再极医药。3大平台，6个在研管线从创立企业的第一天起，王玉光博士就将方向定在恶性肿瘤方向，从药物靶点选择和和药物应用模式两个方面进行创新，开发具有临床治疗差异化的产品。为此，再极医药逐年打造了三大技术平台：口服药物平台、外用药物平台和核素药物平台，依托小分子药物设计优势，突破成熟靶点的边界，寻求差异化竞争。在口服药物平台，再极医药主要开发了重磅管线MAX-40279 和MAX-10181，这是是目前公司进展最快、着重推进的两个管线。● MAX-40279：双靶点抑制治疗急髓性白血病（AML）AML是一种容易复发、难治的高死亡率的恶性血液肿瘤。FLT3是AML的驱动基因，90%以上的AML中FLT3呈现高表达，其中野生型占70%。目前，全球共有3款FLT3抑制剂上市，它们都有单独抑制FLT3靶点，导致FGFR1旁路激活的耐药问题。为了解决这个难题，再极医药开发出FLT3/FGFR1双靶点抑制剂MAX-40279，由天津血研所王建祥教授作为主要研究者领导MAX-40279联合AZA治疗R/R AML Ib/II期临床试验。再极医药的科学与运营高级副总裁冯振华博士在第八届中国医药创新与投资大会全球首发专场上报告的临床数据指出，MAX-40279在联合阿扎胞苷（AZA）的剂量爬坡的临床Ib试验中，取得了对复发难治的FLT3野生型AML的22%的严格的疾病完全缓解CR率，89%的疾病控制DCR率。根据2022年的临床治疗指南，复发难治FLT3野生型AML在全球范围内尚存在空白。王玉光博士还透露，在MAX-40279联合AZA的临床实验中，有一患者经过3个月的治疗，达到了完全疾病缓解CR，顺利完成骨髓移植，康复出院。“可以说，MAX-40279已经展现出了救命药的特征。”● MAX-10181：全球首创口服PD-L1抑制剂与口服化疗药物联合用药“从药物的治疗范围，依从性，可及性、安全性等方面来看，小分子PD-L1抑制剂都具有与抗体药物的差异化。”王玉光博士说。PD-1/L1抗体药物在临床上取得了巨大的成功，成为很多一线治疗的药物。但是，超过70%的患者产生抗体耐药，还需要采用二线，三线等后线治疗。临床I期数据显示，超过60%用过抗体药物的患者，使用MAX-10181进行治疗时，还可以持续获益。因此，MAX-10181和抗体药物组成了治疗肿瘤的接力团队，覆盖不同线数的患者用药。MAX-10181不但可以与抗体药物组成接力团队，还能治疗抗体药物无法治疗的肿瘤。由于抗体的蛋白质理化特性，较难透过血脑屏障，给药效率低，至今未有任何一款PD-1/L1抗体药物获批临床治疗脑胶质瘤。MAX-10181具有血脑屏障穿透能力，在与临床常用的脑胶质瘤治疗化药替莫唑胺的联合用药的动物试验中，取得了优异的结果: 相比替莫唑胺单药，联合MAX-10181提高50%的生存率，具有统计学差异。再极医药已经启动与首都医科大学附属北京天坛医院的著名脑胶质瘤治疗专家李文斌教授合作，探索MAX-10181联合替莫唑胺治疗脑胶质瘤的临床疗效。临床前动物联合用药实验数据和Ⅰ期临床试验结果表明，MAX-10181是一款基石性药物，可以与多种药物进行联合，用于治疗PD-1/L1抗体耐药/不耐受和无法治疗的肿瘤，弥补抗体药物的临床治疗短板。目前，MAX-10181处于临床II期试验，探索联合用药治疗多种实体瘤。就再极医药的外用药物平台而言，外用JAK抑制剂MAX-40070目前处于临床Ⅰ期。在核素药物平台上，再极医药则推动了PD-L1核素诊断项目MAX-20492进入临床IIT研究。其它信息暂未披露。穿越资本寒冬，重点突破领先管线新药研发的“双十定律”至今仍未被打破。但目前来看，无论是时间还是金钱，留给Biotech的都不多了。今年以来，Biotech市场的投融资热情减少，整个行业进入了资本寒冬。据动脉网统计，2023年前三季度，全球与中国生物医药领域的投融资节奏均明显放缓。融资事件上，全球共计发生400件，同比增长3%；中国共计发生128件，同比下降24%。融资额度上，全球总额2587.98亿元，同比下降40%；中国总额361.74亿元，同比下降54%。并且全球已有多家Biotech公司退出市场，截至目前，今年倒闭的美股上市Biotech数量已经超过30家。在生物医药的资本寒冬中，“我们要不忘初心，聚焦研发新药，救治病人。接下来我们会从‘快而广’的管线策略转向‘精而少’，重点推进展现出救命药特征的管线，特别是MAX-40279和MAX-10181，始终为患者服务。”王玉光博士说。“有炎热的夏天当然就有寒冷的冬天，寒冬总是会过去的。”采访的最后王玉光博士补充说。借用英国诗人雪莱的一句话：冬天来了，春天还会远吗？动脉网与再极医药一同期待着属于生物医药的春天。目前，再极医药开启了新一轮融资轮次。文|谢灵微信|shiring821添加时请注明：姓名-公司-职位网站、公众号等转载请联系授权：Rekkiiie近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

AACR会议免疫疗法孤儿药临床1期

2023-11-30

·今日头条

《自然·综述》年度回顾：肠神经系统研究的三大进展

11月30日的《热心肠日报》，我们解读了 10 篇文献，关注：肠神经系统，胃肠道运动，腹痛，生信，真菌，代谢性疾病，口腔菌，肠脑轴，皮肤菌，鱼。 Nature Reviews：肠神经系统的建成、维持和修复（年度回顾） Nature Reviews Gastroenterology and Hepatology——[65.1] ① 在肠神经系统发育过程中，肠神经元从祖细胞向神经胶质细胞分化，成熟的肠胶质细胞保留了早期肠神经系统祖细胞的神经发生特性；② 肌肠丛相关的肌层巨噬细胞从承担早期阶段执行吞噬功能转变为成年肠道中保护肠神经系统的功能；③ 来自人类多能干细胞的迷走神经和骶神经嵴前体产生不同的肠神经元亚型，表现出不同的迁移行为，当它们结合在一起时，可以拯救患有巨结肠疾病的严重小鼠模型。【主编评语】肠道作为人体内最为重要的器官之一，其功能的实现以及与机体其他器官间的相互作用的调节的关键之一是肠神经系统。肠神经系统紊乱与很多肠道相关疾病有着密切的关系，因此在临床治疗中如何有效恢复和重建肠神经系统非常重要。近期一篇发表在Nature Reviews Gastroenterology and Hepatology的综述回顾总结了2023年以来在肠神经系统建立、维持以及修复中的研究进展。（@Zhonghua）【原文信息】 Fresh perspectives on how to build, maintain and repair the ENS 2023-11-17, doi: 10.1038/s41575-023-00870-4 上皮RET信号控制胃肠道运动 Gastroenterology——[29.4] ① 成人肠道中，肠神经元和肠内分泌细胞的不同亚群表达RET；② 在上皮破坏RET，而不是肠神经元中破坏，选择性地减慢雄性小鼠的胃肠道运动，RET激酶抑制剂复现这种现象；③ 大多数RET+上皮细胞是释放5-羟色胺（5-HT）的肠嗜铬细胞，或释放PYY和GLP-1的L-细胞，两种细胞都可改变胃肠道运动性；④ 小鼠和人类类器官中抑制RET激酶，以营养依赖的方式放大PYY和GLP-1的释放，而没有改变5-HT的分泌；⑤ PYY受体阻断挽救上皮缺乏RET小鼠的胃肠道运动障碍。【主编评语】 RET酪氨酸激酶是肠神经系统发育所必需的。RET功能缺失突变导致先天性巨结肠（HSCR），在这种疾病中，婴儿出生时患有无神经节细胞性肠道。尽管进行了手术矫正，但HSCR患者经常会出现慢性排便功能障碍和小肠结肠炎，这表明RET在发育后很重要。Gastroenterology近期发表的文章，发现RET信号通常限制L细胞的营养依赖性肽释放，这种活性对于雄性小鼠的正常肠道蠕动是必需的。这种机制可能解释了一些影响男性的HSCR运动障碍，或可成为一种靶点来治疗餐后胃肠道功能障碍。（@章台柳）【原文信息】 RET Signaling Persists in the Adult Intestine and Stimulates Motility by Limiting PYY Release from Enteroendocrine Cells 2023-11-01, doi: 10.1053/j.gastro.2023.11.020 Science子刊：靶向肠胶质神经元信号传导或可减轻肠炎腹痛 Science Signaling——[7.3] ① 急性结肠炎导致小鼠肠道神经胶质细胞产生IL-1β增加，并增强其细胞间通讯连接蛋白43开放，从而诱导内脏超敏反应；② 诱导小鼠肠炎刺激肠神经胶质细胞分泌前列腺素E2，E2激活肠道神经感觉神经元受体EP4，从而使神经元对原本无害的刺激敏感；③ 无肠炎情况下，激活神经胶质细胞不会刺激神经元或产生内脏疼痛；④ 阻断EP4受体可降低结肠炎小鼠对神经胶质刺激的痛觉感受器敏感性，而损害神经胶质连接蛋白43可降低IL-1β诱导的内脏超敏反应。【主编评语】肠炎会导致腹痛。近日，发表在Science Signaling上的这篇文章，利用急性结肠炎小鼠模型发现肠神经胶质细胞通过分泌使支配肠道感觉神经对炎症敏感的因子而导致内脏疼痛，揭示与炎症特异性相关的肠道疼痛细胞和分子来源，且可能作为治疗靶标。（@圆圈儿）【原文信息】 Enteric glia promote visceral hypersensitivity during inflammation through intercellular signaling with gut nociceptors 2023-11-21, doi: 10.1126/scisignal.adg1668 康禹团队：VTwins可从宏基因组数据中推断致病微生物特征 Science Bulletin——[18.9] ① 通过模仿遗传学研究中的双胞胎研究，开发出VTwins工具通过将原始队列转化为具有不同表型但分类特征匹配的“双胞胎”样本的配对队列来消除混杂效应；② VTwins在识别致病特征的敏感性方面优于传统方法，通过模拟和经验数据测试发现只需减少10倍的样本量就可回忆起与疾病相关的微生物或途径；③ 与其他16种软件的基准测试进一步验证，发现VTwins在宏基因组研究中处理高维组成数据集和挖掘因果关系的能力和适用性较好。【主编评语】由于受到众多混杂因素的干扰，很难从高维宏基因组数据中推断出因果关系。近日，中科院北京基因组研究所康禹及团队在Science Bulletin发表最新研究，开发出VTwins工具（https://github.com/mengqingren/VTwins），发现VTwins在处理高多样性、高维组成数据方面简单有效，可从宏基因组数据中推断致病微生物特征，值得关注。（@九卿臣）【原文信息】 VTwins: inferring causative microbial features from metagenomic data of limited samples 2023-10-28, doi: 10.1016/j.scib.2023.10.024 湖南农大：Clec7a驱动肠道真菌介导的食源性肥胖 Microbiome——[15.5] ① 相比对照组，肥胖猪模型和高脂饮食诱导的肥胖小鼠模型肠道真菌多样性和组成存在显著差异；② 抗真菌药物可保护小鼠免受饮食诱导的肥胖，同居或粪菌移植促进真菌重建可维持HFD小鼠的肥胖表型；③ 鉴定到5个与肥胖相关真菌，其中Ascomycota sp.和Microascaceae sp.与脂肪含量负相关，且参与真菌识别的Clec7a在HFD小鼠中高表达；④ Clec7a激动剂会加速饮食诱导的肥胖，而缺乏Clec7a会对饮食诱导的肥胖产生抵抗，阻断肠道真菌对脂质积累的影响。【主编评语】与细菌相比，肠道真菌在肥胖发展中的作用尚不清楚。近日，湖南农业大学尹杰、肖定福及团队在Microbiome发表最新研究，通过肥胖猪模型和高脂饮食小鼠模型，发现肠道真菌/Clec7a信号会参与饮食诱导的肥胖，未来也可作为人类代谢紊乱的生物标志物，值得关注。（@九卿臣）【原文信息】 Clec7a drives gut fungus-mediated host lipid deposition 2023-11-25, doi: 10.1186/s40168-023-01698-5 广西大学：调节食源性血脂异常时，肠FXR或比肝FXR更重要 Microbiome——[15.5] ① 接受血脂异常供体的粪菌移植（FMT-dd）调节小鼠肠道菌群，诱导血脂异常；② FMT-dd结合高脂饮食可建立饮食诱导人源化血脂异常模型；③ 高脂饮食下FMT-dd诱导的血脂异常经过4周恢复期依然保持，表明饮食诱导人源化血脂异常模型的稳定性；④ 在正常饮食下FMT-dd形成的人源化肠道菌群通过肝脏FXR-SHP轴减少胆汁酸合成并增加胆固醇；⑤ 在高脂饮食下FMT-dd形成的人源化肠道菌群通过肠道FXR-FGF19轴增加胆汁酸合成促进脂质吸收。【主编评语】饮食引起的血脂异常与肠道菌群有关，但肠道菌群与宿主相互作用影响脂质代谢的因果关系仍然存在争议。广西大学高洁团队使用血脂异常供体的粪菌移植成功建立了人源化血脂异常小鼠模型，以研究肠道菌群在饮食诱发的血脂异常中的因果作用，相关成果最新发表在Microbiome上。工作表明基于该模型研究肠道菌群在饮食诱发的血脂异常中的因果作用是可行的，并且揭示肠道菌群-胆汁酸串扰通过肠道FXR而非肝脏FXR介导调节饮食诱发的血脂异常下的脂质代谢。（@RZN）【原文信息】 Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia 2023-11-25, doi: 10.1186/s40168-023-01709-5 上海交大：口腔病原促Th1细胞浸润，加重帕金森病 Microbiome——[15.5] ① 通过MPTP诱导构建PD小鼠模型，结扎诱导牙周炎与龈下菌斑的应用（LIP-SP）会加剧其运动功能障碍、小胶质细胞激活和多巴胺能神经元损失；② LIP-SP会导致小鼠口腔和肠菌失调，联合MPTP处理会增加小韦荣球菌和变形链球菌丰度，促进PD小鼠运动功能障碍和神经退行性恶化；③ 两种致病菌会引起PD小鼠脑内小胶质细胞活化，脑、颈淋巴结、回肠和结肠内Th1细胞浸润；④ 通过IFNγ中和对小韦荣球菌和变形链球菌处理的PD小鼠多巴胺能神经元有保护作用。【主编评语】帕金森病（PD）是一种常见的慢性神经系统疾病，致残风险高且无法治愈。牙周炎是一种发生在牙周支撑组织中的感染性细菌疾病，多项研究已经表明牙周炎与PD密切相关。然而，目前仍缺乏牙周炎对PD影响的直接证据。近日，上海交通大学朱亚琴、段胜仲及团队在Microbiome发表最新研究，发现口腔病原体小韦荣球菌和变形链球菌需要牙周炎的存在，进而加剧MPTP诱导的PD小鼠的运动功能障碍和神经退行性病变，其潜在的机制包括口腔和肠道微生物群的改变，以及大脑和外周区域的免疫激活，值得关注。（@九卿臣）【原文信息】 Oral pathogens exacerbate Parkinson’s disease by promoting Th1 Cell infiltration in mice 2023-11-17, doi: 10.1186/s40168-023-01685-w 芽囊原虫如何影响宿主的行为和情绪？（观点） Trends in Parasitology——[9.6] ① 芽囊原虫是一种常见的肠道寄生虫，通过其蛋白Bh TnaA 结合底物吲哚产生色氨酸；② 芽囊原虫可能通过包括色氨酸前体、5-羟色胺等下游产物及肠道菌群组成的信号网络影响色氨酸；③ 色氨酸代谢在肠道-脑信号通路中发挥作用；④ 芽囊原虫感染直接或间接肠道菌群组成并改变关键代谢产物的水平，可能对宿主行为、认知功能和情绪产生影响；⑤ 提高对肠道内色氨酸和吲哚的认识有助于开发新胃肠道疗法，并减轻芽囊原虫感染风险。【主编评语】近日，发表在Trends in Parasitology上的这篇文章，总结了最近发表的关于芽囊原虫如何影响人类认知和肠道菌群的一系列文章，并提出芽囊原虫可能影响宿主的行为和情绪的潜在作用机制。（@圆圈儿）【原文信息】 Blastocystis: view from atop the gut–brain iceberg 2023-11-16, doi: 10.1016/j.pt.2023.10.002 Cell：金黄色葡萄球菌作用于神经细胞，引发皮肤瘙痒 Cell——[64.5] ① 通过分析特应性皮炎患者样本，发现患者皮肤上金黄色葡萄球菌富集，给小鼠皮下注射该细菌会引起瘙痒和异位反应，但未在皮肤中检测到炎症；② 除普通瘙痒外，小鼠感染区域对其他刺激格外敏感，即使轻微的触摸也会使小鼠产生痒觉；③ 设计多种缺乏特定酶的改造菌株，发现感染缺乏蛋白酶V8菌株的小鼠皮肤不产生瘙痒症状，V8酶会与皮肤神经元PAR1受体结合激活痒觉信号；④ 给感染小鼠使用药物Vorapaxar，能够阻断PAR1受体，消除小鼠的瘙痒症状。【主编评语】湿疹和特应性皮炎引起的瘙痒，通常被认为皮肤炎症引起的。近日，哈佛医学院研究人员在Cell发表最新研究，发现皮肤瘙痒另一个原因是一种常见细菌—金黄色葡萄球菌。这种细菌存在于人类的鼻腔、头发和皮肤上，当免疫力低下时可能会造成感染。大量繁殖的金黄色葡萄球菌会导致皮肤菌群紊乱，并激活痒觉相关信号通路。给感染小鼠使用药物Vorapaxar，能够阻断PAR1受体，消除小鼠的瘙痒症状，值得关注。（@九卿臣）【原文信息】 S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis 2023-11-22, doi: 10.1016/j.cell.2023.10.019 宿主系统发育与肠道和皮肤菌群之间存在显著系统发育共生关系 Microbiome——[15.5] ① 虽然鱼类皮肤和肠道菌群与水中菌群不同，但样本位置（不同河或湖）对所有鱼类的肠道和皮肤菌群的组成都有很强的影响；② 环境、栖息地、鱼类饮食和宿主物种等因素塑造并促进了鱼类菌群的趋同或趋异；③ 鱼类物种效应在系统发育上是一致的，独立于饮食和栖息地，与长期共同进化效应一致；④ 生活在中上层水域的鱼中异常球菌科水平升高，而在深水或底栖鱼类中水平较低，鱼类皮肤和肠道样本中肠杆菌科的水平相对于水样显著升高。【主编评语】虽然许多研究报道皮肤和肠道菌群的结构是由物种特异性和栖息地特异性驱动，但在野生脊椎动物中，宿主特异性与环境因素的相对重要性仍然知之甚少。近期发表于Microbiome上的文章，探究了鱼类皮肤、肠道和周围水体细菌群落的多样性和组成，并评估宿主栖息地和系统发育对菌群相似性的预测程度。结果表明，在宿主相关菌群（肠道和皮肤）的形成和组成方面，宿主所处的环境比宿主特异性选择具有更大的作用，在评估宿主特异性对菌群影响时必须加以考虑。此外，宿主及其相关菌群之间的进化关系也发挥重要作用。（@RZN）【原文信息】 Host species and habitat shape fish-associated bacterial communities: phylosymbiosis between fish and their microbiome 2023-11-20, doi: 10.1186/s40168-023-01697-6 感谢本期日报的创作者：danny，章台柳，圆圈儿，阿童木，accepted，orchid，九卿臣，DM，RZN 点击阅读过去10天的日报： 11-29 | 菌群寻宝：2篇Nature子刊深挖菌群中的抗菌肽 11-28 | 2篇高分研究，挖掘调节免疫的潜在益生菌 11-27 | 20年大队列新证：吃阿司匹林能否降低癌症风险？ 11-26 | Nature子刊：中年开始健康饮食，对寿命的影响有多大？ 11-25 | 善事利器：10文一览菌群研究的新方法和新工具 11-24 | 张发明团队：17页综述讲透粪菌移植前沿进展 11-23 | 今日Nature：两文揭示免疫调控中的饮食和肠道新知 11-22 | 翟齐啸/张家超/黄适Cell子刊突破：改善便秘的关键肠菌遗传因子 11-21 | 30分Cell子刊：一种共生菌或能增强新冠疫苗效果 11-20 | 6文聚焦：癌症的饮食原则和新知

2023-08-10

·BioSpace

Blue Water Biotech and Copay Consultants Collaborate to Build Copay Assistance Programs for Blue Water’s Commercial Products

CINCINNATI, Aug. 10, 2023 (GLOBE NEWSWIRE) -- Blue Water Biotech, Inc. (“Blue Water” or the “Company”), a biotechnology and pharmaceutical company spanning multiple sectors, today announced the signing of an agreement with Copay Consultants, LLC (“Copay Consultants”) to build copay assistance programs for Blue Water’s commercial products, including ENTADFI®, which was acquired in April and ZONTIVITY®, which is expected to be acquired in the coming weeks after the signing of an asset purchase agreement in June. Copay Consultants team has over 40 years of combined experience in the life science industry, including creation of manufacturer sponsored patient savings programs, pharmacy adjudicated copay discount programs, direct to patient rebates, patient web enrollment and attestation services, patient messaging, among others. In this new effort, Blue Water’s commercial team will work closely with Copay Consultants to design and implement a copay assistance program for eligible ENTADFI® and ZONTIVITY® patients. “Oftentimes, getting a prescription and securing insurance coverage is only the first step in the process of a patient initiating therapy,” said Joseph Hernandez, Chairman and Chief Executive Officer of Blue Water. “When patients arrive at the pharmacy and are exposed to high out of pocket costs, copay assistance programs like these can prove critical to ensuring those patients begin treatment. With our copay programs and through this collaboration with Copay Consultants, we are excited to show our commitment to patients across the country and their ability to afford our treatments.” After the acquisition of ENTADFI® in April and signing of an asset purchase agreement to acquire ZONTIVITY® in June, Blue Water management presented its commercial launch strategy in a letter to shareholders last month. Recent execution includes significant progress with Blue Water collaborators and vendors across sales, marketing, advertising, telehealth development, market access, and sample distribution. This new agreement with Copay Consultants is expected to help eligible patients lower the out of pocket costs associated with treatment and is another critical step towards the official launch of these products, expected in the coming months. About ENTADFI® ENTADFI® is an oral, once daily treatment for BPH that combines finasteride, a 5α-reductase inhibitor, and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, offering a more effective treatment option compared to other available therapies. Clinical trials have shown that ENTADFI® is more effective in treating BPH symptoms, including urinary frequency, urgency, weak stream, and difficulty initiating or maintaining urination, compared to finasteride monotherapy. Additionally, ENTADFI® has demonstrated a favorable safety profile, with fewer adverse sexual side effects compared to finasteride. ENTADFI® reduces potential for adverse sexual side effects, making it a preferred choice for men seeking relief from BPH symptoms without compromising their sexual health. ENTADFI® has received FDA approval for the indication of initiating treatment of the signs and symptoms of BPH in men with an enlarged prostate for up to 26 weeks. More information about BPH and full ENTADFI® prescribing information can be found on the product website at About ZONTIVITY® ZONTIVITY® is a once daily, oral treatment indicated for the reduction of thrombotic cardiovascular events for patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). ZONTIVITY® has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization when used with aspirin and/or clopidogrel. More information about MI, PAD, and full ZONTIVITY® prescribing information can be found on the product website at . About Copay Consultants Copay Consultants, LLC is a service provider in the marketing and patient access space within the life science industry. Working as an extension of marketing and market access teams, Copay Consultants develops manufacture sponsored savings programs catered to individual products, market trends and competitive landscape which provide affordable access for patients. For more information about Copay Consultants, visit About Blue Water Biotech Blue Water Biotech, Inc. is a biotechnology and pharmaceutical company focused on developing and commercializing transformational therapies to address significant health challenges globally. Headquartered in Cincinnati, OH, the Company owns ENTADFI®, an FDA-approved, once daily pill that combines finasteride and tadalafil for the treatment of benign prostatic hyperplasia. This combination allows men to receive treatment for their symptoms of benign prostatic hyperplasia without the negative sexual side effects typically seen in patients on finasteride alone. The Company is also in the process of acquiring the approved therapies from WraSer, LLC, and Xspire Pharma, LLC, including ZONTIVITY® (reduction of thrombotic cardiovascular events in patients with myocardial infarction or with peripheral arterial disease), OTOVEL® (acute otitis media with tympanostomy tubes), CETRAXAL® (acute otitis externa), CONJUPRI® (hypertension), TREZIX™ (moderate to severe pain) and NALFON® (NSAID treatment for pain and inflammation). The Company also has a robust preclinical vaccine pipeline. Blue Water holds the rights to proprietary technology developed at the University of Oxford, Cincinnati Children’s Hospital Medical Center, St. Jude Children’s Hospital, and The University of Texas Health Science Center at San Antonio. Blue Water is developing a Streptococcus pneumoniae vaccine candidate, designed to specifically prevent highly infectious middle ear infections, known as AOM, in children, and prevention of pneumonia in the elderly. The Company is also developing a universal flu vaccine that will provide protection from all virulent strains in addition to licensing a novel norovirus S&P nanoparticle versatile virus-like particle vaccine platform from Cincinnati Children’s to develop vaccines for multiple infectious diseases, including Marburg and monkeypox, among others. Additionally, the Company is developing a Chlamydia vaccine candidate with UT Health Science Center San Antonio to prevent infection and reduce the need for antibiotic treatment associated with contracting Chlamydia disease. For more information about Blue Water, visit . Forward-Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements (including, without limitation, the anticipated benefits of the Company’s agreement with Copay Consultants) are based on Blue Water’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, market and other conditions, risks related to Blue Water’s ability to realize the benefits of its acquisitions of ENTADFI®, ZONTIVITY®, OTOVEL®, CETRAXAL®, CONJUPRI®, TREZIX™ and NALFON®; risks related to Blue Water’s ability to expand its business scope, commercialize ENTADFI® and integrate the assets and commercial operations being acquired from WraSer, LLC, and Xspire Pharma, LLC into Blue Water’s business; risks related to Blue Water’s ability to attract, hire and retain skilled personnel and establish an effective sales team; risks related to Blue Water’s ability to establish, maintain and optimize key third party commercial collaboration agreements (such as those with Knipper, UpScript, IQVIA, APS and bfw); risks related to the Company’s present need for capital to close its asset acquisitions, commercially launch the Company’s acquired products and have adequate working capital; risks related to the development of Blue Water’s vaccine candidates; the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the timing and progress of clinical development of our product candidates; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any commercial-stage pharmaceutical product or any product candidate under clinical development, there are significant risks in the development, regulatory approval and commercialization of pharmaceutical products. Blue Water does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Blue Water’s Annual Report on Form 10-K, filed with the SEC on March 9, 2023 and periodic reports filed with the SEC on or after the date thereof. All of Blue Water’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Media Contact Information: Blue Water Media Relations Telephone: (646) 942-5591 Email: Nic.Johnson@russopartnersllc.com Investor Contact Information: Blue Water Investor Relations Email: investors@bwbioinc.com

并购疫苗上市批准

100 项与硫酸沃拉帕沙相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09766	硫酸沃拉帕沙	B01AC26	DB09030

研发状态

适应症	最高研发状态	国家/地区	公司
脑卒中	批准上市	美国更多	Key Therapeutics, LLC初创企业更多
心肌梗塞	批准上市	美国更多	Key Therapeutics, LLC初创企业更多
动脉血栓形成	批准上市	加拿大更多	Xspire Pharma LLC 更多
冠状动脉疾病	批准上市	美国更多	Key Therapeutics, LLC初创企业更多
外周动脉疾病	批准上市	美国更多	Key Therapeutics, LLC初创企业更多

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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


NCT03207451 (CTgov)	临床4期	心肌梗塞 \| 冠心病 \| 外周血管疾病	81	Vorapaxar (Vorapaxar)	蓋壓鑰憲鑰淵窪鬱襯築(壓膚膚鏇簾築獵憲積願) = 鹹鏇廠蓋築艱膚夢壓餘蓋觸製網簾餘餘網憲繭 (顧製築餘積艱選鬱艱範, 簾繭蓋範衊鹹鬱窪繭構 ~ 製築獵顧膚繭繭簾襯遞) 更多	-	2022-08-18
				Clopidogrel (Vorapaxar and Clopidogrel)	蓋壓鑰憲鑰淵窪鬱襯築(壓膚膚鏇簾築獵憲積願) = 蓋繭範鹹網製鏇淵範鬱蓋觸製網簾餘餘網憲繭 (顧製築餘積艱選鬱艱範, 顧蓋遞願鏇鏇選艱餘鑰 ~ 壓餘鑰築網獵鹹壓繭窪) 更多
NCT02545933 (CTgov)	临床4期	陈旧性心肌梗死	130	Vorapaxar+Ticagrelor+Prasugrel+aspirin (DAPT Plus Vorapaxar)	壓觸窪遞襯醖憲壓鏇淵(艱顧襯鬱願築淵製製鬱) = 艱蓋鑰鑰遞繭鹽淵製廠膚鬱築淵範衊廠遞網膚 (糧鹽繭鹹鑰艱糧鹹觸糧, 鏇糧獵糧積廠鹽鬱獵構 ~ 選積築鏇鑰淵積鹽糧構) 更多	-	2020-08-25
				Vorapaxar+Ticagrelor+Prasugrel (Prasugrel/Ticagrelor Plus Vorapaxar)	壓觸窪遞襯醖憲壓鏇淵(艱顧襯鬱願築淵製製鬱) = 醖鬱構製艱網獵顧淵積膚鬱築淵範衊廠遞網膚 (糧鹽繭鹹鑰艱糧鹹觸糧, 獵廠蓋鑰醖廠廠鹽獵齋 ~ 築顧網範構觸夢積膚網) 更多
NCT02475837 (Pubmed \| J Vasc Access) 人工标引	临床2期	动静脉瘘	13	vorapaxar	鹹繭壓網憲糧獵夢鹹餘(積鬱醖簾範齋鏇願願餘) = 鏇鹽簾蓋鬱鬱襯製範蓋鑰窪鏇鹹艱壓夢遞夢壓 (鏇鹹顧艱網鏇衊積夢築 ) 更多	不佳	2020-07-01
				Placebo	鹹繭壓網憲糧獵夢鹹餘(積鬱醖簾範齋鏇願願餘) = 窪鬱選廠鏇鑰鑰艱憲衊鑰窪鏇鹹艱壓夢遞夢壓 (鏇鹹顧艱網鏇衊積夢築 ) 更多
NCT00526474 (TRA 2°P-TIMI 50, Pubmed \| Vasc Med)	临床3期	冠心病 \| 外周动脉疾病	6,136	Vorapaxar	壓壓選觸憲衊積壓壓獵(鏇鹽鬱襯鏇憲膚餘夢製): HR = 0.85 (95% CI, 0.73 ~ 0.99), P-Value = 0.034 更多	-	2020-04-01
				Placebo
NCT02548650 (CTgov)	临床4期	心肌梗塞 \| 外周动脉疾病 \| 糖尿病	66	clopidogrel+Vorapaxar+aspirin (Patients With Diabetes)	夢壓憲選構憲衊願鏇鹽(壓範鹹廠獵醖餘糧鹽蓋) = 製鹹憲淵壓蓋製遞鹹鬱艱壓鏇壓窪艱顧鹽範獵 (夢選餘鹹襯願蓋鑰鹽襯, 繭淵餘窪構簾鏇餘遞膚 ~ 繭網築築範遞鬱醖壓壓) 更多	-	2020-01-27
				clopidogrel+Vorapaxar+aspirin (Patients Without Diabetes)	夢壓憲選構憲衊願鏇鹽(壓範鹹廠獵醖餘糧鹽蓋) = 鑰築觸鏇簾網範鹽醖淵艱壓鏇壓窪艱顧鹽範獵 (夢選餘鹹襯願蓋鑰鹽襯, 鹹膚淵艱鏇夢範鹹艱憲 ~ 繭鹹積蓋膚簾築襯蓋壓) 更多
NCT02875028 (CTgov)	临床4期	内毒素血症	16	LPS+Vorapaxar (Vorapaxar)	窪夢窪觸糧糧積壓構醖(壓願醖積獵繭淵夢製醖) = 餘齋範醖構願襯製顧醖齋糧鏇艱淵鏇糧製壓糧 (鏇襯鏇網蓋憲遞齋鏇鹽, 窪糧獵網觸觸鏇窪選鑰 ~ 廠鬱艱蓋淵積繭繭衊襯) 更多	-	2020-01-10
				LPS (Placebo)	窪夢窪觸糧糧積壓構醖(壓願醖積獵繭淵夢製醖) = 鏇遞衊廠壓範襯築壓壓齋糧鏇艱淵鏇糧製壓糧 (鏇襯鏇網蓋憲遞齋鏇鹽, 淵淵製艱鹽餘鏇鏇築顧 ~ 蓋築壓膚襯範淵鬱醖繭) 更多
NCT02394730 (CTgov)	临床1/2期	HIV肠病 \| 凝血障碍	65	vorapaxar (Vorapaxar)	淵糧顧製範鏇鬱築鏇襯(顧鏇選網壓壓齋鹹膚齋) = 觸製鏇廠艱鹽窪製蓋顧壓艱選網鹹齋鬱壓鏇餘 (糧鬱簾鏇遞糧構壓網觸, 衊襯繭觸膚齋鬱範製構 ~ 餘鏇憲齋網觸糧範積鹽) 更多	-	2019-02-28
				Placebo (Placebo)	淵糧顧製範鏇鬱築鏇襯(顧鏇選網壓壓齋鹹膚齋) = 醖鑰積鏇鏇壓鑰醖鹹餘壓艱選網鹹齋鬱壓鏇餘 (糧鬱簾鏇遞糧構壓網觸, 鑰願鹽醖餘夢鹽範壓艱 ~ 鬱範網淵夢艱蓋鬱簾鑰) 更多
NCT02475837 (CTgov)	临床2期	动静脉瘘	17	Vorapaxar sulfate (Vorapaxar Intervention)	糧製醖鬱選壓鏇夢餘獵(艱夢簾遞鑰壓糧夢選糧) = 鏇網構選構醖選糧夢觸淵鏇蓋獵遞衊憲鏇顧窪 (膚選範窪鏇鑰壓齋鹹觸, 顧鬱遞廠餘餘壓醖壓選 ~ 選夢選選網觸構遞繭製) 更多	-	2019-01-14
				placebo (Placebo Intervention)	糧製醖鬱選壓鏇夢餘獵(艱夢簾遞鑰壓糧夢選糧) = 範範憲願鏇簾鏇衊廠網淵鏇蓋獵遞衊憲鏇顧窪 (膚選範窪鏇鑰壓齋鹹觸, 範觸憲蓋蓋夢鏇襯顧顧 ~ 鏇壓餘鑰築廠壓壓觸蓋) 更多
NCT02394730 (ADVICE, Pubmed) 人工标引	临床1/2期	炎症 \| HIV感染 \| 凝血障碍	65	vorapaxar	壓鹽膚鬱築糧鹹窪鏇壓(鏇獵繭網顧齋壓蓋願餘): difference = -0.02 (95% CI, -0.10 ~ 0.05), P-Value = 0.56	积极	2018-10-01
				Placebo
TRA2Â°P-TIMI-50 (ESC2018)	N/A	冠心病 soluble P-selectin \| TAT \| IXa-AT ... 更多	-	Vorapaxar	遞鏇簾窪窪艱蓋糧憲艱(醖繭繭憲廠願艱願鏇憲) = 製鏇窪製襯餘膚壓鑰遞積鑰鬱網獵鏇觸齋膚觸 (鑰製願範夢繭齋簾鑰積 ) 更多	-	2018-08-25
				Placebo	遞鏇簾窪窪艱蓋糧憲艱(醖繭繭憲廠願艱願鏇憲) = 鹽膚襯鏇廠觸獵淵築淵積鑰鬱網獵鏇觸齋膚觸 (鑰製願範夢繭齋簾鑰積 ) 更多