Clinical Trials Register

Summary
EudraCT Number:	2011-004666-15
Sponsor's Protocol Code Number:	TMC-MDC-11-01
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-11-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2011-004666-15

A.3

Full title of the trial

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

Eine kontrollierte, doppelblinde Phase II Studie zur Dosis-Wirkungs-Findung des antifibrinolytischen Prüfmedikamentes MDCO-2010 im Vergleich mit Placebo und Tranexamsäure bei Patienten mit primärer Herzoperation

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Dose section Phase II study to compare the inhibition of blood loss in patients undergoing primary heart surgery and treatment with the investigational drug MDCO-2010, the active comparator tanexamic acid or placebo.

Dosisfindungsstudie zum Vergleich des klinischen Prüfmusters MDCO 2010, mit dem Vergleichspräparat Tranexamsäure oder Placebo bezüglich der Reduzierung des Blutverlusts bei Herzoperationen.

A.4.1

Sponsor's protocol code number

TMC-MDC-11-01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	The Medicines Company
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	The Medicines Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	The Medicines Company (Leipzig) GmbH
B.5.2	Functional name of contact point	Managing Director
B.5.3	Address:
B.5.3.1	Street Address	Deutscher Platz 5d
B.5.3.2	Town/ city	Leipzig
B.5.3.3	Post code	D-04103
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49089244180862
B.5.5	Fax number	+49089244180889
B.5.6	E-mail	andreas.locht@THEMEDCO.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MDCO-2010
D.3.2	Product code	MDCO-2010
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	MDCO-2010
D.3.9.3	Other descriptive name	3-HOOC-Bzls-D-Ppg-Phe(3-Ame)-4-Amba acetate
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Cyklokapron Injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Cyklokapron Injection
D.3.2	Product code	Cyklokapron Injection
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1197-18-8
D.3.9.3	Other descriptive name	TRANEXAMIC ACID
D.3.9.4	EV Substance Code	SUB11214MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Primary cardiac surgery involving cardiopulmonary bypass

E.1.1.1

Medical condition in easily understood language

Cardiac surgery

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of this study is to determine the dose response relationship regarding blood loss, pharmacokinetics (PK), pharmacodynamics (PD), safety and clinical outcomes of MDCO-2010 vs. placebo and tranexamic acid in patients undergoing primary cardiac surgery

E.2.2

Secondary objectives of the trial

safety

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

ROTEM SUBSTUDY, Thrombelastography/Thrombelastometry allows an overall assessment of hemostatic function. It provides a graphic representation of both, clot formation and lysis.
Rotation thrombelastometry (ROTEM) is now widely accepted as point-of-care assessment of the viscoelastic clot strength in whole blood and is thus regarded as a clinically relevant model to investigate both coagulation and fibrinolysis [Gallimore et al, 2005]. ROTEM has been shown to detect changes in fibrinolysis in humans [Spiel et al, 2006].
The objectives of the ROTEM substudy are to determine parameters of coagulation and fibrinolysis in whole blood over the course of surgery and study drug administration.
The substudy is part of the protocol TMC-MDC-11-01 Version 2.0, Date 31.10.2011

E.3

Principal inclusion criteria

• In Stage 1: Planned primary isolated CABG surgery
• In Stage 2: Planned primary isolated CABG surgery, OR Planned primary combined CABG and aortic valve replacement surgery
• Men, aged 18 to 85 years, OR
Women, aged 18 to 85 years, either of postmenopausal status, defined as ≥1 year since last menstrual period, or with a medical history of hysterectomy or bilateral oophorectomy
•Written informed consent

E.4

Principal exclusion criteria

• Off-pump surgery or hybrid procedures
• Patients undergoing repeat sternotomy
• Planned deep hypothermic circulatory arrest (<28°C)
• Known allergy, sensitivity or contraindications to tranexamic acid
• Epileptiform disorders, history of seizure activity or anticonvulsive medication
• Administration of clopidogrel, ticagrelor or ticlopidine within 5 days prior to surgery or prasugrel within 7 days prior to surgery
• Administration of low molecular weight heparin, glycoprotein IIb/IIIa inhibitors or fondaparinux within 12 hours prior to surgery
• Known history of coronary stent thrombosis within the last 3 months
• History of stroke or transient ischemic attack within 3 months prior to surgery
• Left ventricular ejection fraction (LVEF) ≤35% or Grade III or IV
• Body mass index <20 or >35
• Known active gastrointestinal (GI) or other non-catheterization bleeding within 7 days prior to surgery
• Preoperative coagulation abnormalities defined as:
– Platelet count <100,000/L or >350,000/L, or
– International normalized ratio (INR) >1.5, or
– Hematocrit <36%, or
– Activated partial thromboplastin time (aPTT) >1.5 x the upper limit of normal (ULN)
• Major surgical procedures within 30 days prior to surgery
• Patient inability or refusal to receive donor blood products if necessary
• Creatinine >2 mg/dL or estimated glomerular filtration rate (eGFR) (calculated using Modification of Diet in Renal Disease [MDRD] equation) <30 mL/min
• Known heparin-induced thrombocytopenia type II
• Known history of thrombophilia, such as AT-III, Protein C or Protein S deficiency, Factor V Leiden, anti-phospholipid syndrome
• Known active liver disease
• Any condition requiring ongoing chronic immunosuppressive medication
• Malignancy within 5 years prior to surgery
• Receipt of an investigational drug or device within 60 days prior to surgery
• Any other condition which, in the opinion of the Principal Investigator, would put the subject at increased risk from participating in the study or otherwise prevent a patient’s participation in the study

E.5 End points

E.5.1

Primary end point(s)

• Chest tube drainage 12 hours after surgery

E.5.1.1

Timepoint(s) of evaluation of this end point

12 hours after surgery

E.5.2

Secondary end point(s)

Efficacy:
• Chest tube drainage at 6 and 24 hours postoperatively
• Avoidance of any transfusions
• Incidence of massive postoperative transfusion, defined as >5 units of red blood cells (RBCs) within 24 hours postoperatively
• Number of allogeneic blood product (RBC, FFP or PC) units transfused within 24 hours postoperatively
• Incidence of re-sternotomy for bleeding or cardiac tamponade within 24 hours postoperatively
• Incidence of requirement for mechanical ventilation longer than 24 hours postoperatively
• Time to extubation
• Length of intensive care unit (ICU) stay
Safety:
• Occurrence of death within 30 days post-treatment
• Occurrence of myocardial infarction within 30 days post-treatment
• Occurrence of stroke within 30 days post-treatment
• Incidence of convulsive seizures within 7 days post-treatment
• Incidence of deep vein thrombosis or pulmonary embolism within 7 days post-treatment
• Incidence of acute kidney injury
• Incidence of clinically significant biomarker changes indicative of renal (creatinine), cardiac (troponin) and hepatic (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [Alk P] and bilirubin) function
• All adverse events (AEs) and serious adverse events (SAEs)
Pharmacokinetic and pharmacodynamic:
• Pharmacokinetic
– MDCO-2010 plasma and urine concentrations to calculate PK parameters
• Pharmacodynamic
– D-dimer
– aPTT and ACT

E.5.2.1

Timepoint(s) of evaluation of this end point

throughout treatment and follow-up

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Switzerland

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

135

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

135

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

130

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

270

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will only undergo study specific investigations and treatments described in this protocol. No further investigations will be performed after hospital discharge. Any investigations or treatments performed after discharge will be done at the sole discretion of the investigator or treating physician.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials