Clinical Trials Register

Summary
EudraCT Number:	2014-001661-27
Sponsor's Protocol Code Number:	ISSBRIL0162
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-10-16
Trial 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

2014-001661-27

A.3

Full title of the trial

Comparison of TIcagrelor and clopidogrel in patients with Coronary artery diseaSe and type 2 Diabetes Mellitus (TICS-DM): a randomized pharmacodynamic study

Comparación entre Ticagrelor y Clopidogrel en pacientes con cardiopatía isquémica y Diabetes Mellitus tipo 2 (TICS-DM): Un estudio farmacodinámico aleatorizado

A.3.1

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

Comparison of ticagrelor and clopidogrel in patients with diabetes mellitus and ischemic heart disease

Comparación entre ticagrelor y clopidogrel en pacientes con diabetes mellitus y enfermedad isquémica del corazón

A.3.2

Name or abbreviated title of the trial where available

TICS-DM

A.4.1

Sponsor's protocol code number

ISSBRIL0162

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	Sociedad Española de Cardiología
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sociedad Española de Cardiología
B.5.2	Functional name of contact point	Asuntos científicos e investigación
B.5.3	Address:
B.5.3.1	Street Address	Nuestra Señora de Guadalupe 5
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28028
B.5.3.4	Country	Spain
B.5.4	Telephone number	34917242370237
B.5.6	E-mail	ifernandez@secardiologia.es

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	Brilique 90mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca
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.3.4	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	Ticagrelor
D.3.9.3	Other descriptive name	TICAGRELOR
D.3.9.4	EV Substance Code	SUB30898
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	90
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	Plavix 75 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Clir SNC
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.3.4	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	Clopidogrel
D.3.9.3	Other descriptive name	CLOPIDOGREL
D.3.9.4	EV Substance Code	SUB13395MIG
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	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.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

Coronary artery disease

Enfermedad arterial coronaria

E.1.1.1

Medical condition in easily understood language

Narrowing of coronary arteries that can cause lack of oxygen supply to the heart producing chest pain and infarction

Estrechamiento de las arterias coronarias que puede causar falta de aporte de oxígeno al corazón produciendo dolor torácico e infarto

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 primary objective of the present study is to compare platelet inhibitory effects achieved after one week of treatment with ticagrelor versus clopidogrel, both on top of aspirin therapy, in patients with type 2 diabetes mellitus and coronary artery disease

El objetivo primario de este estudio es comparar la inhibición plaquetar alcanzada tras una semana de tratamiento con ticagrelor frente a clopidogrel, asociados a ácido acetilsalicílco, en pacientes con Diabetes Mellitus tipo 2 y cardiopatía isquémica

E.2.2

Secondary objectives of the trial

1. To assess the pharmacodynamic impact of ticagrelor and clopidogrel loading and maintenance doses in type 2 diabetes mellitus patients, measured with different platelet function assays
2. To compare the percentage of patients with low-responsiveness to either ticagrelor or clopidogrel therapy.

1. Evaluar el impacto farmacodinámico de la dosis carga y de mantenimiento de ticagrelor y clopidogrel en pacientes con diabetes mellitus tipo 2, medidos con diferentes tests de función plaquetar
2. Comparar el porcentaje de pacientes con baja respuesta a ticagrelor o clopidogrel

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Provision of informed consent prior to any study specific procedures
2. Age between 18 and 75 years
3. Type 2 diabetes mellitus according to ADA criteria
4. Angiographically documented coronary artery disease
5. Chronic treatment (>1 month) with aspirin (100mg/day)

1. Firma del consentimiento informado antes de recibir cualquier tratamiento o procedimiento específico del estudio.
2. Edad entre 18 y 75 años.
3. Diabetes mellitus tipo 2 de acuerdo a los criterios de la ADA.
4. Cardiopatía isquémica confirmada por angiografía.
5. Tratamiento crónico (>1 mes) con aspirina (100mg/día).

E.4

Principal exclusion criteria

1. Known allergies to aspirin, clopidogrel, or ticagrelor
2. Blood dyscrasia or bleeding diathesis
3. Any recent acute coronary syndrome (<30 days) or hemodinamic instability
4. Recent antiplatelet therapy (<14 days), with the exception of ASA, including: thienopyridines, cilostazol, dipiridamol, glycoprotein IIb/IIIa inhibitors
5. Oral anticoagulation with a coumarin derivative
6. Any active bleeding
7. Recent history of stroke, transient ischemic attack or intracranial bleeding (<6 months prior to inclusion)
8. Platelet count <100x106/microl
9. Any active neoplasm
10. Severe chronic kidney disease (creatinine clearance measured with Cockcroft-Gault formula <30ml/min)
11. Baseline ALT >2.5 times the upper limit of normality
12. Pregnant or childbearing females

1. Alergias a aspirina, clopidogrel o ticagrelor.
2. Discrasias sanguíneas.
3. Cualquier síndrome coronario agudo reciente (<30 días) o inestabilidad hemodinámica.
4. Tratamiento antiplaquetar reciente (<14 días), con la excepción de aspirina, incluyendo: tienopiridinas, cilostazol, dipiridamol, inhibidores de la glicoproteína IIb/IIIa.
5.Anticoagulación oral con un derivado cumarínico.
6. Hemorragia activa.
7. Historia reciente de ictus, accidente isquémico transitorio o hemorragia intracraneal (<6 meses previos al período de inclusión).
8. Recuento plaquetar <100x106/microl.
9. Insuficiencia renal severa, definida como filtrado glomerular (fórmula de Cockcroft-Gault) <30mL/min.
10. Neoplasia activa.
11. ALT basal superior a 2,5 veces el límite normal de la normalidad.
12. Gestación.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the comparison of the degree of maximal platelet aggregation, measured with light transmittance aggregometry (using 20 ?M ADP as agonist), achieved after 1 week of treatment

El end point primario es la comparación en la máxima agregación plaquetar, medida con agregometría óptica (utilizando 20microM de ADP como agonista), alcanzada tras una semana de tratamiento

E.5.1.1

Timepoint(s) of evaluation of this end point

After 1 week of treatment with ticagrelor compared to clopidogrel

Tras 1 semana de tratamiento con ticagrelor comparado con clopidogrel

E.5.2

Secondary end point(s)

Assessment of platelet reactivity after 1 week of treatment with ticagrelor compared with clopidogrel (maintenance dose) measured by: a) Analysis of phosphorilation of vasodilator-stimulated phosphoprotein; b) VerifyNow system; c) Multiple electrode aggregometry
Assesment of platelet reactivity after a loading dose of ticagrelor compared to clopidogrel with all platelet funtion assays performed

Evaluación de la reactividad plaquetar tras 1 semana de tratamiento con ticagrelor comparado con clopidogrel (dosis mantenimiento) medida con: a) Análisis de la fosforilación de la vasodilator-stimulated phosphoprotein; b) VerifyNow system; c) Agregometría de electrodos múltiples
Evaluación de la reactividad plaquetar tras dosis de carga de ticagrelor comparado con clopidogrel con todos los tests de función plaquetar empleados

E.5.2.1

Timepoint(s) of evaluation of this end point

Loading dose: 2 hours and 24 hours
Maintenance dose: 1 week

Dosis de carga: 2 horas y 24 horas
Dosis de mantenimiento: 1 semana

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

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

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

Última visita del último sujeto incluido

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

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:

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

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.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

2014-12-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-04

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

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