Delving into the Latest Updates on CU-2010 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Serine protease

Mechanism

Serine protease inhibitors

Therapeutic Areas

Cardiovascular DiseasesOther Diseases

Active Indication-

Inactive Indication

Coronary Artery DiseaseHemorrhage

Originator Organization

The Medicines Company (Spain) SL

Active Organization-

Inactive Organization

The Medicines Co.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC37H42N6O6S

InChIKeyBHQDUYVBGREBCB-SAIUNTKASA-N

CAS Registry1021707-76-5

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.

Start Date01 Mar 2012

Sponsor / Collaborator

The Medicines Co.

NCT01535222 / CompletedPhase 2

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.

Start Date01 Nov 2010

Sponsor / Collaborator

The Medicines Co.

100 Clinical Results associated with CU-2010

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100 Translational Medicine associated with CU-2010

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100 Patents (Medical) associated with CU-2010

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5

Literatures (Medical) associated with CU-2010

01 Jul 2014·Anesthesia & AnalgesiaQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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.

01 Aug 2012·Anesthesia & AnalgesiaQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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.

01 Mar 2010·The Journal of Thoracic and Cardiovascular SurgeryQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: Matthias Karck ; Gábor Veres ; Andreas van de Locht ; Nelli Krieger ; Humaira Haider ; Tamás Radovits ; Susanne Bährle ; Silke Niklisch ; Gábor Szabó ; 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 Deals associated with CU-2010

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemorrhage	Phase 2	CH	The Medicines Co.	01 Mar 2012
Hemorrhage	Phase 2	DE	The Medicines Co.	01 Mar 2012
Coronary Artery Disease	Phase 2	-	The Medicines Co.	01 Nov 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01530399 (CTgov)	Phase 2	Hemorrhage	44	MDCO 1 (MDCO 1)	vzkmnupnrx(wcgkgbapxf) = efteehdqbg rjeylpdpvo (etupocdcny, eyvtzxlqar - fhpvznfukx) View more	-	10 Dec 2015
				MDCO 2 (MDCO 2)	vzkmnupnrx(wcgkgbapxf) = rpgcafomcr rjeylpdpvo (etupocdcny, bjjcwaytrs - ddtycegzte) View more
NCT01535222 (CTgov)	Phase 2	Coronary Artery Disease	32	MDCO-2010 (Cohort 1)	xxktepylvl(vaeuwzpjqs) = sauciexmem gfxxqndlcm (yqmszwrgfj, kezlzpxrda - justuunddc) View more	-	19 Jul 2012
				MDCO-2010 (Cohort 2)	xxktepylvl(vaeuwzpjqs) = eynkknsbjq gfxxqndlcm (yqmszwrgfj, bllzybxkzs - ewtxbismeu) View more