Clinical Trials Register

Summary
EudraCT Number:	2016-002681-31
Sponsor's Protocol Code Number:	BAY1213790/17664
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-05-23
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2016-002681-31

A.3

Full title of the trial

A randomized, active-comparator-controlled, multicenter study to assess the safety and efficacy of different doses of BAY 1213790 for the prevention of venous thromboembolism in patients undergoing elective primary total knee arthroplasty, open-label to treatment and observer-blinded to BAY 1213790 doses

Ensayo clínico aleatorizado, controlado con comparador activo, multicéntrico, abierto para el tratamiento y ciego para el observador para las dosis de BAY1213790, para evaluar la seguridad y la eficacia de diferentes dosis de BAY1213790 en la prevención del tromboembolismo venoso en pacientes sometidos a una artroplastia de reemplazo total de rodilla.

A.3.1

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

A study to investigate BAY 1213790 of different doses to prevent blood clot in patients having elective total knee replacement surgery

Ensayo clínico para investigar diferentes dosis de BAY 1213790 en la prevención de formación de trombos sanguíneos en pacientes sometidos a una artroplastia de reemplazo total de rodilla.

A.3.2

Name or abbreviated title of the trial where available

FOXTROT

A.4.1

Sponsor's protocol code number

BAY1213790/17664

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	Bayer AG
B.1.3.4	Country	Germany
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	Bayer AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	0034.900 102372
B.5.6	E-mail	clinical-trials-contact@bayer.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	BAY 1213790
D.3.2	Product code	BAY 1213790
D.3.4	Pharmaceutical form	Lyophilisate for solution for 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.3.8	INN - Proposed INN	N/A
D.3.9.2	Current sponsor code	BAY 1213790
D.3.9.3	Other descriptive name	BAY 1213790
D.3.9.4	EV Substance Code	SUB187446
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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	Clexane
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS LIETUVA, UAB, Lietuva
D.2.1.2	Country which granted the Marketing Authorisation	Lithuania
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	enoxaparin
D.3.2	Product code	enoxaparin 40 mg/0.4 ml, sol. for inj.
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ENOXAPARIN SODIUM
D.3.9.1	CAS number	9041-08-1
D.3.9.2	Current sponsor code	Enoxaparin
D.3.9.3	Other descriptive name	Enoxaparin
D.3.9.4	EV Substance Code	SUB11933MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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: 3
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	Eliquis
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb/Pfizer EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	apixaban
D.3.2	Product code	apixaban 2.5 mg
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	APIXABAN
D.3.9.1	CAS number	503612-47-3
D.3.9.2	Current sponsor code	Apixaban
D.3.9.3	Other descriptive name	Apixaban
D.3.9.4	EV Substance Code	SUB25425
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of venous thromboembolism

Prevención del tromboembolismo venoso

E.1.1.1

Medical condition in easily understood language

Prevention of blood clot in the veins

Prevención de la coagulación de la sangre en las venas

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10049909
E.1.2	Term	Venous thromboembolism prophylaxis
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety and efficacy of different doses of BAY 1213790 in comparison with those of enoxaparin in patients undergoing elective, primary, unilateral total knee arthroplasty (TKA)

Evaluar la seguridad y la eficacia de diferentes dosis de BAY 1213790 en comparación con las dosis de enoxaparina en pacientes sometidos a una artroplastia total programada, primaria y unilateral de rodilla (ATR).

E.2.2

Secondary objectives of the trial

To compare the safety and efficacy of BAY 1213790 with those of apixaban

Comparar la seguridad y la eficacia de BAY 1213790 con apixaban

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients aged >= 8 years undergoing elective primary, unilateral TKA
• Women of non-childbearing potential

- Pacientes >= 18 años sometidos a una ATR programada primaria y unilateral
- Mujeres sin capacidad reproductora

E.4

Principal exclusion criteria

• High risk for clinically significant bleeding or any of the following conditions:
o Anemia (Hb <10 g/dL in women, < 11 g/dL in men) at Screening
o Platelet count at Screening < 150 x 109/L or history of heparin-induced thrombocytopenia
o aPTT or PT (INR or Quick) > ULN at Screening
o Hepatic disease associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase (ALT) > 3x upper level of normal (ULN) or total bilirubin (TB) > 2x ULN with direct bilirubin > 20% of the total at Screening
o Brain, spinal, or ophthalmologic surgery (except cataract surgery) within 3 months prior to randomization
o Known bleeding disorders
• Prior deep vein thrombosis
• Creatinine clearance below 60 ml/min, calculated by MDRD formula at Screening
• Active cancer except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been curatively treated
• Contraindication listed in the local label of the comparator treatments
• Requirement for full dose anticoagulation or dual antiplatelet therapy (low dose of acetylsalicylic acid is allowed)

• Riesgo elevado de hemorragia clínicamente significativa o cualquiera de las patologías siguientes:
o Anemia (Hb < 10 g/dl en mujeres, < 11 g/dl en hombres) en el momento de la selección
o Cifra de plaquetas en el momento de la selección < 150 x 109/l o antecedentes de trombocitopenia inducida por heparina
o TTPa o TP (INR o Quick) > Límite superior de normalidad (LSN) en el momento de la selección
o Hepatopatía asociada a: coagulopatía que conlleva riesgo de hemorragia clínicamente relevante, o alanina-aminotransferasa (ALT) > 3 veces el (LSN o bilirrubina total (BT) > 2 veces el LSN con bilirrubina directa > 20 % del total en la selección
o Cirugía cerebral, de columna u oftalmológica (excepto cirugía de cataratas) en los 3 meses anteriores a la aleatorización
o Trastornos hemorrágicos conocidos
• Trombosis venosa profunda previa
• Aclaramiento de creatinina inferior a 60 ml/min, calculado según la fórmula MDRD en la selección
• Cáncer activo excepto carcinoma de piel de células basales o escamosas o carcinoma in situ del cuello uterino para el que se haya recibido tratamiento curativo
• Contraindicaciones que se incluyen en la ficha técnica local de los tratamientos comparadores
• Necesidad de tratamiento anticoagulante con dosis completas o doble antiagregación (se permiten dosis bajas de ácido acetilsalicílico)

E.5 End points

E.5.1

Primary end point(s)

• Incidence of asymptomatic DVT, detected by mandatory bilateral venography, and objectively confirmed symptomatic DVT or non-fatal PE (symptomatic VTE), fatal PE and unexplained death for which PE cannot be excluded

• Incidence of major and clinically relevant non-major bleeding

• Incidencia de TVP asintomática, detectada por flebografía bilateral obligatoria, y TVP sintomática confirmada objetivamente, o EP no mortal, EP mortal y muerte sin causa aparente para la cual no se puede excluir la EP

• Hemorragias graves y no graves clínicamente relevantes

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 7, Day 12+3

Visita 7, dia 12+3

E.5.2

Secondary end point(s)

• Incidence of symptomatic DVT or non-fatal PE (symptomatic VTE), fatal PE and unexplained death for which PE cannot be excluded up to Visit 10 (Day 150±7) or objectively confirmed asymptomatic DVT up to
Visit 7 (Day 12+3)

• Incidence of major and clinically relevant non-major bleeding

• Incidencia de TVP sintomática o EP no mortal (TVP sintomática), EP mortal y muerte sin causa aparente para la cual no se puede excluir la EP hasta la Visita 10 (día 150±7) o TVP asintomática confirmada objetivamente hasta la Visita 7 (día 12+3)

• Hemorragias graves y no graves clínicamente relevantes

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 10, Day 150±7

Visita 10, Día 150±7

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

abierto para el tratamiento y ciego para el observador para las dosis de BAY1213790

open-label for the assignment to the study drugs, observer blinded to the dose of BAY1213790

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Bulgaria

Canada

Czech Republic

Germany

Greece

Hungary

Israel

Latvia

Lithuania

Poland

Russian Federation

South Africa

Spain

Ukraine

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

LVLS

Último sujeto última visita

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:

350

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

350

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

540

F.4.2.2

In the whole clinical trial

700

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)

None

Ninguno

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-01-02

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IMP with orphan designation in the indication
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