Clinical Trials Register

Summary
EudraCT Number:	2019-003244-79
Sponsor's Protocol Code Number:	20603
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:	2019-12-20
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

2019-003244-79

A.3

Full title of the trial

Multicenter, randomized, placebo controlled, double-blind, parallel group, dose-finding Phase 2 study to evaluate the efficacy and safety of BAY 2433334 in patients following an acute myocardial infarction

Ensayo de fase II, multicéntrico, aleatorizado, controlado con placebo, doble ciego, de grupos paralelos, de búsqueda de dosis para evaluar la eficacia y seguridad de BAY 2433334 en pacientes que han sufrido un infarto agudo de miocardio.

A.3.1

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

Study to gather information about the proper dosing and safety of the oral FXIa inhibitor BAY 2433334 in patients following an acute heart attack

Ensayo para recopilar información sobre la dosis adecuada y la seguridad del inhibidor oral de FXIa, BAY 2433334, en pacientes después de haber sufrido un ataque al corazón.

A.3.2

Name or abbreviated title of the trial where available

PACIFIC-AMI

A.4.1

Sponsor's protocol code number

20603

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	Müllerstrasse 178
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
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 2433334
D.3.2	Product code	BAY 2433334
D.3.4	Pharmaceutical form	Film-coated 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	NA
D.3.9.1	CAS number	2064121-65-7
D.3.9.2	Current sponsor code	BAY 2433334 TABL 5 MG 201 COAT
D.3.9.3	Other descriptive name	BAY 2433334
D.3.9.4	EV Substance Code	SUB187352
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	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.IMP: 2
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 2433334
D.3.2	Product code	BAY 2433334
D.3.4	Pharmaceutical form	Film-coated 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	NA
D.3.9.1	CAS number	2064121-65-7
D.3.9.2	Current sponsor code	BAY 2433334 TABL 15 MG 301 COAT
D.3.9.3	Other descriptive name	BAY 2433334
D.3.9.4	EV Substance Code	SUB187352
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	15
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	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 2433334
D.3.2	Product code	BAY 2433334
D.3.4	Pharmaceutical form	Film-coated 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	NA
D.3.9.1	CAS number	2064121-65-7
D.3.9.2	Current sponsor code	BAY 2433334 TABL 25 MG 401 COAT
D.3.9.3	Other descriptive name	BAY 2433334
D.3.9.4	EV Substance Code	SUB187352
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	25
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	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute Myocardial Infarction

Infarto Agudo de Miocardio

E.1.1.1

Medical condition in easily understood language

Acute heart attack that happens when a blood vessel in the heart suddenly becomes blocked

Ataque de corazón que ocurre cuando un vaso sanguíneo en el corazón se bloquea repentinamente

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10064939
E.1.2	Term	Cardiovascular event prophylaxis
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 evaluate whether the oral FXIa inhibitor BAY 2433334 compared to placebo leads to a lower incidence of cardiovascular (CV) death, MI, stroke and stent thrombosis in participants with an acute myocardial infarction and who are treated with dual antiplatelet therapy.
• To evaluate whether the incidence of bleeding is similar for BAY 2433334 compared to placebo in participants with an acute myocardial infarction and who are treated with dual antiplatelet therapy.

• Evaluar si el inhibidor oral de FXIa BAY 2433334 en comparación con el placebo conduce a una menor incidencia de muerte cardiovascular (CV), infarto de miocardio (IM), ictus y trombosis del stent en participantes con un infarto agudo de miocardio y que reciben tratamiento antiagregante plaquetario doble.
•Evaluar si la incidencia de hemorragias es similar con BAY 2433334 en comparación con placebo en participantes con infarto agudo de miocardio y que reciben tratamiento antiagregante plaquetario doble.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participants must be 45 years of age or older, at the time of signing the informed consent
2. Acute myocardial infarction (excluding MI associated with PCI or CABG revascularization procedures) with:
a.clinical symptoms of acute myocardial infarction AND
b.elevated biomarkers of myocardial necrosis (creatine kinase-muscle and brain isoenzyme [CK-MB] or cardiac troponins) AND
c.at least one of the following risk factors need to be fulfilled:
i. Age ≥ 65 years
ii.Prior MI (before the index AMI event)
iii.Prior peripheral arterial disease
iv.Diabetes Mellitus
v.Prior coronary artery bypass grafting (CABG)
AND
d. initial angiography and revascularization procedures, either PCI or CABG, as treatment for the index event performed before randomization. (Note: a planned, staged PCI procedure can be performed after randomization)
3. Plan for dual antiplatelet therapy (ASA + P2Y12 inhibitor) after hospital discharge for the index AMI
4. Randomization during hospitalization for the index AMI event and latest within 5 days of hospital admission
5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent has to be signed before any study-specific procedure.

1. Los participantes deben tener una edad igual o superior a 45 años en el momento de firmar el consentimiento informado.
2. Infarto agudo de miocardio (excluido el IM asociado a procedimientos de revascularización mediante ICP o CABG (por siglas en inglés de coronary artery bypass grafting) con:
a. síntomas clínicos de infarto agudo de miocardio Y
b. biomarcadores elevados de necrosis miocárdica (isoenzima creatincinasa muscular y cerebral [CK-MB] o troponinas cardíacas) Y
c. Al menos uno de los siguientes factores de riesgo debe cumplirse:
i. Edad ≥65 años
ii. IM previo (antes del IAM de referencia)
iii. Arteriopatía periférica previa
iv. Diabetes mellitus
v. Cirugía de derivación aortocoronaria (CABG) previo
Y
d. procedimientos iniciales de angiografía y revascularización, ya sea ICP o GABG, como tratamiento para el evento de referencia realizados antes de la aleatorización.
3. Planificación de tratamiento antiagregante plaquetario doble (AAS + inhibidor de P2Y12) después del alta hospitalaria por el IAM de referencia.
4. Aleatorización durante la hospitalización por el IAM de referencia y como máximo en los 5 días posteriores al ingreso.
5. Capacidad para otorgar el consentimiento informado firmado que incluye el cumplimiento de los requisitos y restricciones enumerados en el formulario de consentimiento informado y en este protocolo. El consentimiento informado por escrito debe firmarse antes de realizar cualquier procedimiento específico del estudio.

E.4

Principal exclusion criteria

1. Hemodynamically significant ventricular arrhythmias or cardiogenic shock at time of randomization
2. Active bleeding; known bleeding disorder, history of major bleeding (intracranial, retroperitoneal, intraocular) or clinically significant gastrointestinal bleeding within last 6 months of randomization
3. Planned use or requirement of full dose and long term anticoagulation therapy during study conduct

1. Choque cardiógeno o arritmias ventriculares de relevancia hemodinámica en el momento de la aleatorización.
2. Hemorragia activa; trastorno hemorrágico conocido, antecedentes de hemorragia grave (intracraneal, retroperitoneal, intraocular) o hemorragia gastrointestinal de relevancia clínica en los 6 meses previos a la aleatorización.
3. Uso planificado o necesidad de anticoagulación de dosis completa y a largo plazo durante la realización del estudio

E.5 End points

E.5.1

Primary end point(s)

Efficacy Endpoint
Time from randomization to first occurrence of any of the components of the composite outcome including CV death, MI, stroke and stent thrombosis
Safety Endpoint:
Time from randomization to first occurrence of Bleeding Academic Research Consortium (BARC) bleeding definition type 2, 3 and 5

Variable Principal de Eficacia:
Tiempo desde la aleatorización hasta la primera aparición de cualquiera de los componentes de la combinación, incluida la muerte CV, infarto de miocardio, ictus y la trombosis del stent.
Variable Principal de Seguridad:
Tiempo desde aleatorización hasta la primera aparición de hemorragia de Bleeding Academic Research Consortium (BARC) tipos 1, 2, 3 y 5

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline up to 12 months

Desde el inicio hasta los 12 meses

E.5.2

Secondary end point(s)

Efficacy Endpoints:
1. Time from randomization to death (all cause mortality)
2. Time from randomization to CV death
3. Time from randomization to first occurrence of MI
4. Time from randomization to first occurrence of stroke (ischemic and hemorrhagic)
5. Time from randomization to first occurrence of stent thrombosis
Safety Endpoints:
1. Time from randomization to first occurrence of all bleeding
2. Time from randomization to first occurrence of BARC bleeding definition Type 3, 5
3. Time from randomization to first occurrence of BARC bleeding definition Type 1, 2, 3, 5

Variable Principal de Eficacia:
1. Tiempo desde la aleatoriación hasta la muerte (mortalidad por todas las causas)
2. Tiempo desde la aleatorización hasta la muerte CV
3. Tiempo desde la aleatorización hasta la primera aparición del IM
4. Tiempo desde la aleatorización hasta la primera aparición de ictus (isquémico y hemorrágico)
5. Tiempo desde la aleatorización hasta la primera aparición de trombosis del stent
Variable Principal de Seguridad:
1. Tiempo desde la aleatorización hasta la primera de todas las hemorragias
2. Tiempo desde la aleatorización hasta la definición de hemorragia de BARC tipos 3 y 5
3. Tiempo desde la aleatorización hasta la definición de hemorragia de BARC tipos 1, 2, 3 y 5

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline up to 12 months

Desde el inicio hasta los 12 meses

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers

Biomarcadores

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)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Busqueda de dosis

Dose-finding

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

120

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

Austria

Belgium

Canada

Czech Republic

Germany

Hungary

Italy

Japan

Netherlands

Poland

Spain

Swaziland

Sweden

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

LVLS

Ultima visita del ultimo paciente

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:

800

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

800

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

196

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1120

F.4.2.2

In the whole clinical trial

1600

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

Ninguna

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

2020-02-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-15

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
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