Clinical Trials Register

Summary
EudraCT Number:	2014-004189-64
Sponsor's Protocol Code Number:	HI-TECH
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-11-05
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-004189-64

A.3

Full title of the trial

Hunting for the OFF-target properties of Ticagrelor on endothelial function and other circulating biomarkers in humans

Alla ricerca delle propriet¿ fuori prescrizione del Ticagrelor: funzione endoteliale e altri biomarcatori circolanti nell'uomo

A.3.1

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

Discovering new clinical properties of ticagrelor

Ricerca su nuove propriet¿ cliniche di ticagrelor

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

HI-TECH

A.5.4

Other Identifiers

Name:

Number:

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	ERASMUS MC
B.1.3.4	Country
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	Erasmus MC - Rotterdam
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione IRCCS Policlinico San Matteo
B.5.2	Functional name of contact point	Cardiologia
B.5.3	Address:
B.5.3.1	Street Address	P.le Golgi 19
B.5.3.2	Town/ city	Pavia
B.5.3.3	Post code	27100
B.5.4	Telephone number	+39 0382 987983
B.5.5	Fax number	+39 0382 987984
B.5.6	E-mail	s.leonardi@smatteo.pv.it

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 - 90 MG - COMPRESSE RIVESTITE CON FILM - USO ORALE - BLISTER(PVC/PVDC/ALU) 60 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA AB
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.9.1	CAS number	274693-27-5
D.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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 50 COMPRESSE FILMRIVESTITE 75 MG IN BLISTER
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI PHARMA BRISTOL-MYERS SQUIBB SNC
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.9.1	CAS number	113665-84-2
D.3.9.2	Current sponsor code	NA
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	EFIENT - 5MG - COMPRESSA RIVESTITA CON FILM - USO ORALE BLISTER (ALL) 30X1 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	ELI LILLY NEDERLAND BV
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	PRASUGREL
D.3.9.1	CAS number	150322-43-3
D.3.9.2	Current sponsor code	NA
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	10
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Acute coronary syndrome

Sindrome coronarica acuta

E.1.1.1

Medical condition in easily understood language

Acute coronaric syndrome

Sindrome coronarica acuta

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	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 assess whether Ticagrelor, at steady state, is associated to an improved endothelial function as compared to clopidogrel or prasugrel.

Verificare se il Ticagrelor, a regime terapeutico, ¿ associato ad un miglioramento della funzione endoteliale rispetto a Clopidogrel e Prasugrel

E.2.2

Secondary objectives of the trial

To investigate the effect of the P2Y12 inhibitors on the following
¿ Clinical endpoint: cardiovascular death, myocardial infarction or stroke, fatal or non-fatal ischemic attack or TIA and bleedings
¿ Biochemical endpoints: the reactive hyperemia index (RHI) 1-2 hour(s) after the oral P2Y12 inhibitor loading, asymmetrical dimethylarginine (ADMA), micro-albuminuria, von willebrand factor antigen, C-reactive protein, soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)], residual platelet reactivity assessed at verifynow in terms of PRU and ARU, and effect of P2Y12 oral blocker on endothelial function, prothrombin fragment 1+2, fibrinopeptide A and thrombin¿antithrombin complex (TAT) adenosine plasma concentration (APC), Ticagrelor and AR-C124910XX.

Studiare l¿effetto degli inibitori P2Y12 su:
¿ Endpoint clinici: decesso cardiovascolare, infarto del miocardio o ictus, attacco ischemico o attacco ischemico transitorio (TIA) fatale o non fatale e sanguinamenti.
¿ Endpoint biochimici: Reactive Hyperemia Index(RHI) 1-2 ore dopo la dose di carico orale dell¿inibitore P2Y12, dimetilarginina asimmetrica (ADMA), microalbuminuria, fattore von Willebrand, proteina C reattiva, sFLT-1, ICAM-1,VCAM-1, reattivit¿ piastrinica residua individuata con ¿Verifynow¿ in termini di PRU e ARU, l¿effetto degli inibitori orali di P2Y12 sulla funzione endoteliale, frammento protrombina 1+2, fibrinopeptide A e TAT (complesso trombina-antitrombina), APC (concentrazione plasmatica adenosina), e Ticagrelor AR-C124910XX

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects older than 18 years old, who experienced an ACS (including STEMI or NSTEMI) at least 30 days before, with an going treatment for at least 30 days with dual anti-platelet therapy consisting of aspirin + commercially available P2Y12 oral inhibitor, including ticagrelor, clopidogrel or prasugrel at on-label maintenance regimen who remained free from bleeding or ischemic recurrences.

Soggetti di età = 18 anni, che hanno avuto un episodio di ACS (incluso STEMI o NSTEMI) almeno 30 gg prima, in terapia DAPT da almeno 30 gg con aspirina + inibitore del P2Y12 (ticagrelor, clopidogrel, prasugrel), libero da sanguinamento e da ricorrenza di eventi ischemici.

E.4

Principal exclusion criteria

Administration of fibrinolytics or glycoprotein IIb/IIIa inhibitors in the previous 30 days, major surgery within 30 days or any planned surgical intervention, active bleeding or previous clinical relevant bleeding or stroke in the last 6 months, previous intracranial bleeding, thrombocytopenia, oral anticoagulant therapy, vasculitis or any know immunological disorder, severe hepatic failure, uncontrolled hypertension (systolic or diastolic arterial pressure >180 mmHg or 120, respectively, despite medical therapy), known intolerance to aspirin or to clopidogrel or prasugrel or ticagrelor, limited life expectancy, e.g. neoplasms, others, inability to obtain informed consent, pregnant and breastfeeding women, patients taking potent inhibitors of the CYP3A4. Women of childbearing potential must use appropriate contraception to avoid pregnancy during therapy.

Pazienti a cui siano stati somministrati fibrinolitici o inibitori della glicoproteina IIb / IIIa nei 30 giorni precedenti, chirurgia maggiore entro 30 giorni o qualsiasi intervento chirurgico programmato, sanguinamento attivo o precedente sanguinamento clinico rilevante, ictus negli ultimi 6 mesi, precedente sanguinamento intracranico, trombocitopenia, terapia anticoagulante orale, vasculite o qualsiasi disordine immunologico, insufficienza epatica grave, ipertensione non controllata (pressione arteriosa sistolica> 180 mmHg o diastolica>120 mmHg rispettivamente, nonostante la terapia medica), l'intolleranza nota ad aspirina o clopidogrel o prasugrel o ticagrelor, l'aspettativa di vita limitata, ad esempio, neoplasie. Sono inoltre escluse le donne in gravidanza e in allattamento; le donne fertili devono usare un appropriato metodo contraccettivo. Sono infine esclusi i pazienti che assumono potenti inibitori di CYP3A4.

E.5 End points

E.5.1

Primary end point(s)

The reactive hyperemia index (RHI) at treatment steady state (30-days), assessed with endopath system (Endopath; Itamar Medical Ltd., Cesarea, Israel).

Reactive hyperemia index (RHI) a regime terapeutico (30-giorni), misurato con il sisitema Endopath (Endopath; Itamar Medical Ltd., Cesarea, Israel).

E.5.1.1

Timepoint(s) of evaluation of this end point

3 months

3 mesi

E.5.2

Secondary end point(s)

See secondary objectives

Vedi obiettivi secondari

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of study

A fine studio

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

Yes

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)

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

Yes

E.8.2.3.1

Comparator description

Clopidogrel (IMP2); Prasugrel (IMP1)

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.8.4.1

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

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:

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

After the trial, patient will continue the original treatment, unless treating physician prefers otherwise

Al termine dello studio, il soggetto continuer¿ il trattamento che stava assumendo prima dello studio, salvo diversa preferenza del medico

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

2015-11-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-04-09

P. End of Trial
P.	End of Trial Status	Ongoing

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