(CU-2010) - 药物靶点：Serine protease_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Serine protease

作用机制

丝氨酸蛋白酶家族抑制剂

治疗领域

心血管疾病其他疾病

在研适应症-

非在研适应症

手术失血冠心病出血

原研机构

The Medicines Company (Spain) SL

在研机构-

非在研机构

The Medicines Co.The Medicines Company (Spain) SL

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)-

特殊审评-

结构

分子式C37H42N6O6S

InChIKeyBHQDUYVBGREBCB-SAIUNTKASA-N

CAS号1021707-76-5

关联

3

项与 CU-2010 相关的临床试验

EUCTR2011-004666-15-DE / Not yet recruiting临床2期

A Phase II, double-blind, parallel group, dose-selection study to compare antifibrinolytic MDCO-2010 vs. placebo and tranexamic acid in reducing blood loss in patients undergoing primary cardiac surgery

开始日期-

申办/合作机构

The Medicines Co.

NCT01530399 / Terminated临床2期

A Phase II, Double-blind, Parallel Group, Dose-selection Study to Compare Antifibrinolytic MDCO-2010 vs. Placebo and Tranexamic Acid in Reducing Blood Loss in Patients Undergoing Primary Cardiac Surgery

The objective of this study is to determine the dose response relationship regarding blood loss, PK, PD and clinical outcomes of MDCO-2010 in comparison to placebo and tranexamic acid in patients undergoing primary cardiac surgery with cardiopulmonary bypass. The aim of the study is to define minimally effective dose of MDCO-2010.

开始日期2012-03-01

申办/合作机构

The Medicines Co.

NCT01535222 / Completed临床2期

A Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MDCO-2010 in Patients Undergoing Elective CABG Surgery

The purpose of this study is to demonstrate that periprocedural infusion of escalating doses of MDCO-2010 is safe and tolerated in patients undergoing elective CABG surgery, to characterize the single dose pharmacokinetics of MDCO-2010, to investigate the effect of MDCO-2010 on pharmacodynamics (biomarkers of fibrinolysis and coagulation parameters), and to investigate the effect on exploratory clinical endpoints of bleeding, transfusion requirements and reexploration.

开始日期2010-11-01

申办/合作机构

The Medicines Co.

100 项与 CU-2010 相关的临床结果

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100 项与 CU-2010 相关的转化医学

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100 项与 CU-2010 相关的专利（医药）

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5

项与 CU-2010 相关的文献（医药）

2014-07-01·Anesthesia & Analgesia2区 · 医学

A Novel Blood-Sparing Agent in Cardiac Surgery? First In-Patient Experience with the Synthetic Serine Protease Inhibitor MDCO-2010

2区 · 医学

Article

作者: Englberger, Lars ; Dietrich, Wulf ; Eberle, Balthasar ; Carrel, Thierry ; Keller, Dorothee ; Erdoes, Gabor

BACKGROUNDAntifibrinolytics have been used for 2 decades to reduce bleeding in cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We describe the first experience with this drug in patients.METHODSIn this phase II, double-blind, placebo-controlled study, 32 patients undergoing isolated primary coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to 1 of 5 increasing dosage groups of MDCO-2010. The primary aim was to evaluate pharmacokinetics (PK) with assessment of plasmatic concentrations of the drug, short-term safety, and tolerance of MDCO-2010. Secondary end points were influence on coagulation, chest tube drainage, and transfusion requirements.RESULTSPK analysis showed linear dosage-proportional correlation between MDCO-2010 infusion rate and PK parameters. Blood loss was significantly reduced in the 3 highest dosage groups compared with control (P = 0.002, 0.004 and 0.011, respectively). The incidence of allogeneic blood product transfusions was lower with MDCO-2010 4/24 (17%) vs 4/8 (50%) in the control group. MDCO-2010 exhibited dosage-dependent antifibrinolytic effects through suppression of D-dimer generation and inhibition of tissue plasminogen activator-induced lysis in ROTEM analysis as well as anticoagulant effects demonstrated by prolongation of activated clotting time and activated partial thromboplastin time. No systematic differences in markers of end organ function were observed among treatment groups. Three patients in the MDCO-2010 groups experienced serious adverse events. One patient experienced intraoperative thrombosis of venous grafts considered possibly related to the study drug. No reexploration for mediastinal bleeding was required, and there were no deaths.CONCLUSIONSThis first-in-patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of chest tube drainage and transfusions in patients undergoing primary coronary artery bypass grafting. Antifibrinolytic and anticoagulant effects were demonstrated using various markers of coagulation. MDCO-2010 was well tolerated and showed an acceptable initial safety profile. Larger multi-institutional studies are warranted to further investigate the safety and efficacy of this compound.

2012-08-01·Anesthesia & Analgesia2区 · 医学

The Effects of MDCO-2010, a Serine Protease Inhibitor, on Activated Clotting Time in Blood Obtained from Volunteers and Cardiac Surgical Patients

2区 · 医学

Article

作者: Jerrold H. Levy ; Heezoo Kim ; Fania Szlam ; Satoru Ogawa ; Andreas van de Locht ; Kenichi A. Tanaka

BACKGROUNDThe activated clotting time (ACT) is widely used for monitoring heparin anticoagulation during cardiac surgery. Celite-based ACT values are prolonged when aprotinin is administered. MDCO-2010, a novel serine protease inhibitor, is currently being evaluated as a possible alternative to aprotinin. Therefore, we evaluated the in vitro effects of this novel agent on ACT values using 3 different point-of-care instruments with kaolin or celite as an activator.METHODSThe study was performed in 2 parts. In the first part, blood samples were obtained from 15 healthy volunteers. Samples were pipetted into small Eppendorf tubes and 2 concentrations of the MDCO-2010 (100 and 500 nM, final concentration) alone or with heparin (1.2 or 2.4 U/mL) were added. ACTs were measured using Helena (celite), Hemochron (kaolin), and Medtronic (kaolin) devices. In the second part of the study, blood samples were obtained intraoperatively, at 5 time points, from 15 patients undergoing cardiopulmonary bypass. MDCO-2010 at a final concentration of 100 or 500 nM was added and ACT testing was performed as before. Additional coagulation tests included prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, prothrombin, and anti-Xa levels.RESULTSAddition of MDCO-2010 concentration-dependently prolonged ACTs in volunteers' and patients' blood samples regardless of the ACT activator or device used. In volunteer samples (no heparin) and in patient samples (baseline and intensive care unit) percent changes in ACTs due to MDCO-2010 were on average 3.1 ± 1.8 times higher (95% confidence interval 2.6-3.6; P < 0.001) for the celite-based Helena device compared with either Hemochron or Medtronic devices.CONCLUSIONMDCO-2010 causes less ACT prolongation with kaolin than with celite activation.

2010-03-01·The Journal of Thoracic and Cardiovascular Surgery1区 · 医学

The novel synthetic serine protease inhibitor CU-2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery after cardiac surgery in a canine model

1区 · 医学

Article

作者: Matthias Karck ; Gábor Veres ; Andreas van de Locht ; Nelli Krieger ; Humaira Haider ; Tamás Radovits ; Gábor Szabó ; Susanne Bährle ; Silke Niklisch ; Christiane Miesel-Gröschel

BACKGROUNDSerine protease inhibitors such as aprotinin reduce perioperative blood loss and may improve postpump cardiac performance owing to their anti-inflammatory properties. After the "aprotinin era," we investigated the efficacy of the novel synthetic serine protease inhibitors CU-2010 with improved coagulatory and anti-inflammatory profile on blood loss and reperfusion injury in a canine model.METHODSThirty-six dogs were divided into 6 groups: control, aprotinin (n = 8; Hammersmith scheme), and CU-2010 (0.5, 0.83, 1.25, and 1.66 mg/kg). All animals underwent 90 minutes of cardiopulmonary bypass with 60 minutes of hypothermic cardioplegic arrest. End points were blood loss during the first 2 hours after application of protamine, as well as recovery of myocardial contractility (slope of the end-systolic pressure-volume relationship, coronary blood flow, and vascular reactivity.RESULTSCU-2010 dose-dependently reduced blood loss to a degree comparable with that of aprotinin at lower doses and even further improved at higher doses (control/aprotinin/CU-2010 in increasing doses: 142 +/- 13, 66 +/- 17, 95 +/- 16, 57 +/- 17, 46 +/- 3, and 13 +/- 4 mL; P < .05). Whereas aprotinin did not influence myocardial function, CU-2010 improved the recovery of end-systolic pressure-volume relationship (control 60 +/- 6 mg kg vs aprotinin 73 +/- 7 mg/kg vs CU-2010 1.66 mg/kg; 102% +/- 8%; P < .05). Coronary blood flow (52 +/- 4 vs 88 +/- 7 vs 96 +/- 7; P < .05) and response to acetylcholine (44% +/- 6% vs 77% +/- 7% vs 81% +/- 6%; P < .05) were improved by both aprotinin and CU-2010.CONCLUSIONSThe novel serine protease inhibitor CU-2010 significantly reduced blood loss after cardiac surgery comparable with aprotinin. Furthermore, an additionally improved anti-inflammatory profile led to a significantly improved postischemic recovery of myocardial and endothelial function.

100 项与 CU-2010 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
出血	临床2期	德国	The Medicines Co.	2012-03-01
出血	临床2期	瑞士	The Medicines Co.	2012-03-01
冠心病	临床2期	-	The Medicines Co.	2010-11-01
手术失血	临床2期	瑞士	The Medicines Co.	-
手术失血	临床2期	-	The Medicines Company (Spain) SL	-
手术失血	临床2期	德国	The Medicines Co.	-

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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


NCT01530399 (CTgov)	临床2期	出血	44	MDCO 1 (MDCO 1)	築選鏇憲醖獵淵鹽鏇簾(醖憲觸願衊膚築繭憲衊) = 範夢範鑰鏇鹹蓋簾鬱淵鑰餘鑰範醖糧衊襯願糧 (鹽顧窪窪糧鹽簾襯齋鏇, 鑰鹽獵鏇範簾夢廠蓋壓 ~ 鹹衊選醖製願願餘繭廠) 更多	-	2015-12-10
				MDCO 2 (MDCO 2)	築選鏇憲醖獵淵鹽鏇簾(醖憲觸願衊膚築繭憲衊) = 鏇繭窪獵顧艱鹹衊艱壓鑰餘鑰範醖糧衊襯願糧 (鹽顧窪窪糧鹽簾襯齋鏇, 鑰鹽壓選鹹鏇糧淵夢範 ~ 獵餘蓋鬱鹽夢鏇鑰夢襯) 更多
NCT01535222 (CTgov)	临床2期	冠心病	32	MDCO-2010 (Cohort 1)	(糧鹹餘繭壓簾艱鏇製壓) = 糧繭憲艱衊鹽蓋選艱淵夢壓選糧獵齋構淵鬱膚 (顧餘壓鹹齋積築襯製憲, 獵鏇膚鹹齋膚窪齋膚獵 ~ 餘襯齋積鹽衊齋壓襯鬱) 更多	-	2012-07-19
				MDCO-2010 (Cohort 2)	(糧鹹餘繭壓簾艱鏇製壓) = 網遞鑰積壓淵範糧繭醖夢壓選糧獵齋構淵鬱膚 (顧餘壓鹹齋積築襯製憲, 憲觸壓蓋鹹壓築襯襯襯 ~ 夢鹽衊積醖膚遞艱膚鹹) 更多