Clinical Trials Register

Summary
EudraCT Number:	2014-004266-26
Sponsor's Protocol Code Number:	BAY59-7939/RIVAROXACS2002/17896
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-03-18
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-004266-26

A.3

Full title of the trial

A Randomized, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multicenter Study to Compare the Safety of Rivaroxaban versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Subjects with Acute Coronary Syndrome

Uno studio randomizzato, in doppio cieco e in doppio placebo, controllato attivamente, a gruppi paralleli, multicentrico per confrontare la sicurezza di Rivaroxaban rispetto all'acido acetilsalicilico in aggiunta alla terapia con clopidogrel o ticagrelor in soggetti con sindrome coronarica acuta.

A.3.1

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

A Study to Compare the Safety of Rivaroxaban versus Acetylsalicylic Acid in Addition to Either
Clopidogrel or Ticagrelor Therapy in Participants with Acute Coronary Syndrome

Uno studio per confrontare la sicurezza di Rivaroxaban rispetto all'acido acetilsalicilico in aggiunta alla terapia con clopidogrel o ticagrelor in soggetti con sindrome coronarica acuta.

A.3.2

Name or abbreviated title of the trial where available

GEMINI ACS 1

A.4.1

Sponsor's protocol code number

BAY59-7939/RIVAROXACS2002/17896

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	Janssen-Cilag International NV
B.1.3.4	Country	Belgium
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	Janssen Research & Development, LLC
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	Janssen Research and Development, LLC
B.5.2	Functional name of contact point	Alexei Plotnikov, M.D.
B.5.3	Address:
B.5.3.1	Street Address	920 Route 202 South
B.5.3.2	Town/ city	Raritan, NJ
B.5.3.3	Post code	08869
B.5.3.4	Country	United States
B.5.4	Telephone number	+1908927 7792
B.5.6	E-mail	APlotnik@its.jnj.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	Yes
D.2.1.1.1	Trade name	XARELTO®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Pharma AG
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	rivaroxaban 2.5 mg
D.3.2	Product code	JNJ-39039039; BAY59-7939
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	RIVAROXABAN
D.3.9.1	CAS number	366789-02-8
D.3.9.2	Current sponsor code	JNJ-39039039; BAY 59-7939
D.3.9.4	EV Substance Code	SUB29263
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.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	Aspirin®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmbH
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	Aspirin 100 mg
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	Aspirin
D.3.9.1	CAS number	50-78-2
D.3.9.3	Other descriptive name	ACETYLSALICYLIC ACID
D.3.9.4	EV Substance Code	SUB12730MIG
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	100
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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-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 Coronary Syndrome (ACS)

Sindrome coronarica acuta

E.1.1.1

Medical condition in easily understood language

Heart attack

Attacco di cuore

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10051592
E.1.2	Term	Acute coronary syndrome
E.1.2	System Organ Class	10007541 - Cardiac disorders

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 estimate the bleeding risk with rivaroxaban compared with ASA, in addition to a single antiplatelet agent (a platelet adenosine diphosphate P2Y12 receptor antagonist [P2Y12 inhibitor], clopidogrel or ticagrelor), in subjects with a recent ACS (including ST-segment elevation myocardial infarction [STEMI] and non-ST-segment elevation acute coronary syndrome [NSTE-ACS]).

Per valutare il rischio di emorragia con rivaroxaban, in confronto ad ASA, in aggiunta a un singolo agente antipiastrinico (un recettore piastrinico antagonista di adenosina difosfato P2Y12 [inibitore P2Y12], clopidogrel o ticagrelor), in soggetti con evento recente di SCA (incluso infarto miocardico con elevazione del segmento ST [STEMI] e sindrome coronarica acuta senza elevazione del segmento ST [SCA-NSTE]).

E.2.2

Secondary objectives of the trial

NAP

nap

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Participants, 18 years or older, must have symptoms suggestive of acute coronary syndrome (ACS) (angina, or symptoms thought to be equivalent) within 48 hours of hospital presentation, or developed ACS while being hospitalized, and has a diagnosis of: a) ST segment elevation myocardial infarction (STEMI);
b) non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, participant who is 54 years of age or younger must also have either diabetes mellitus or a history of a prior myocardial infarction (MI), in addition to the presenting ACS event
- Participant must be randomized within the screening window of 10 days after hospital admission for the index ACS event. Participant should have received acute phase treatment for the index ACS, such as intravenous anticoagulant or antiplatelet, and are receiving maintenance dual antiplatelet therapy (DAPT) with either clopidogrel plus acetyl salicylic acid (ASA), or ticagrelor plus ASA, with the intent to continue the treatment with a platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor) after randomization
- Participants must agree to provide a pharmacogenomics deoxyribonucleic acid (DNA) sample

Il soggetto, di anni 18 o più, deve presentare sintomi che suggeriscono SCA (angina o sintomi considerati analoghi) nell'arco di 48 ore dalla presentazione all'ospedale o deve aver sviluppato la SCA durante il ricovero presentare una diagnosi di a) STEMI elevazione del segmento ST b) non elevazione ST (NSTE-ACS). Il soggetto di età uguale o inferiore a 54 anni di età deve presentare anche diabete mellito o un precedente di IM in aggiunta all'evento di SCA attuale.

-Il soggetto deve essere randomizzato entro la finestra di screening di 10 giorni dopo il ricovero in ospedale per l'evento indice di SCA. Il soggetto deve aver ricevuto un trattamento endovenoso nella fase acuta per la SCA indice, con un anticoagulante oppure un antipiastrinico e sta ricevendo la DAPT di mantenimento con clopidogrel più ASA o ticagrelor più ASA, con l'intenzione di continuare il trattamento con l'inibitore P2Y12 dopo la randomizzazione;

Tutti i soggetti devono impegnarsi a fornire un campione di DNA per l'analisi farmacogenomica.

E.4

Principal exclusion criteria

- Participant has any conditions that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk
- Participant with a prior stroke of any etiology or transient ischemic attack (TIA)
- Participant who received thrombolytic therapy as treatment for the index ACS event cannot be enrolled in the ticagrelor stratum
- Participant has anticipated need for chronic administration of omeprazole or esomeprazole concomitantly with clopidogrel
- Participant has known allergy or intolerance to ASA or rivaroxaban

- Il soggetto presenta qualsiasi condizione che, secondo il giudizio dello sperimentatore, controindicherebbe una terapia anticoagulante o presenterebbe un rischio non accettabile.
-Il soggetto ha condizioni precedenti o patologie gravi concomitanti quali precedente di ictus di qualunque eziologia o TIA

Il soggetto che ha ricevuto una terapia trombolitica come trattamento per l'evento di SCA non può essere arruolato nello strato ticagrelor.
-Il soggetto presenta una necessità supposta di somministrazione cronica di inibitori della pompa protonica in concomitanza con clopidogrel.
-Il soggetto ha allergie o intolleranza note a ASA o rivaroxaban.

E.5 End points

E.5.1

Primary end point(s)

Number or Participants with Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events

Numero di partecipanti con Trombolisi nell'Infarto Miocardico (TIMI) con sanguinamento clinicamente significativo

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to Day 390

Fino a 390 giorni

E.5.2

Secondary end point(s)

NAP

nap

E.5.2.1

Timepoint(s) of evaluation of this end point

NAP

nap

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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

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

Yes

E.8.1.7.1

Other trial design description

Double-dummy

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

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

159

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

Argentina

Australia

Belgium

Bulgaria

Canada

Czech Republic

Denmark

France

Germany

Hungary

Italy

Japan

Korea, Republic of

Netherlands

Poland

Russian Federation

Spain

Sweden

Turkey

Ukraine

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 DELL'ULTIMO SOGGETTO

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

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:

2940

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1524

F.4.2.2

In the whole clinical trial

3000

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)

Not different from the standard treatment of the condition

Non diversa dalla normale pratica clinica

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

2015-04-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-14

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

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