Clinical Trials Register

Summary
EudraCT Number:	2015-002755-94
Sponsor's Protocol Code Number:	CV185-391
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-02-05
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

2015-002755-94

A.3

Full title of the trial

MicroRNAs and target genes modulation in subjects with atrial fibrillation treated with apixaban or warfarin

Modulazione dell¿espressione di microRNA e geni target in soggetti con fibrillazione atriale trattati con Apixaban o Warfarin.

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

AMO-M

A.4.1

Sponsor's protocol code number

CV185-391

A.5.4

Other Identifiers

Name:

AMO-M

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	FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
B.1.3.4	Country	Italy
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	BMS
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FONDAZIONE POLICLINICO GEMELLI
B.5.2	Functional name of contact point	AREA CARDIOVASCOLARE
B.5.3	Address:
B.5.3.1	Street Address	L.GO GEMELLI 8
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00168
B.5.3.4	Country	Italy
B.5.4	Telephone number	0630154187
B.5.5	Fax number	063055535
B.5.6	E-mail	comitato.etico@policlinicogemelli.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	No
D.2.1.1.1	Trade name	ELIQUIS - 5 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PVC/PVDC/ALU) - 20 COMPRESSE
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	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.3.1	Product name	Eliquis
D.3.2	Product code	[041225069]
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	apixaban
D.3.9.1	CAS number	503612-47-3
D.3.9.2	Current sponsor code	2015-002755-94
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2 to 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	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	COUMADIN - 5 MG COMPRESSE 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL MYERS SQUIBB S.R.L.
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.3.1	Product name	coumadin
D.3.2	Product code	[016366027]
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	coumadin
D.3.9.1	CAS number	81-81-2
D.3.9.2	Current sponsor code	2015-002755-94
D.3.10	Strength
D.3.10.1	Concentration unit	1X 100 milligrams/millilitre
D.3.10.2	Concentration type	up to
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	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

Atrial fibrillation

Fibrillazione atriale

E.1.1.1

Medical condition in easily understood language

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	10001452
E.1.2	Term	AFib
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary Objective of this prospective randomized study is to assess whether Apixaban significantly modifies microRNA involved in:1- coagulation 2- left ventricle and atrium function, 3- atrial fibrillation as compared to standard therapy with Warfarin. A population of 50 patients with ischemic heart disease and/or type 2 diabetes (T2DM) will be randomized to Apixaban or Warfarin to evaluate differences in the expression of specific circulating microRNAs before and after treatment. The primary end-point is to test whether the differences of the top three differentially expressed microRNA involved in coagulation between patients randomized to Apixaban and Warfarin at 3-month follow-up are statistically significant (p < 0.05).

stabilire se Apixaban, rispetto alla terapia anticoagulante standard con Warfarin, sia in grado di modificare in maniera significativa i microRNAs coinvolti in: 1- coagulazione; 2- funzione atriale e ventricolare sinistra, 3- fibrillazione atriale. Una popolazione di 50 pazienti con cardiopatia ischemica e/o DM tipo 2 (T2DM) sar¿ randomizzata ad assumere Apixaban o Warfarin per valutare differenze nell¿espressione di specifici microRNA circolanti prima e dopo il trattamento. L¿end-point primario dello studio ¿ valutare se la differenza esistente tra i livelli di espressione dei primi 3 microRNAs coinvolti nella cascata coagulativa tra i pazienti randomizzati ad Apixaban e a Warfarin dopo 3 mesi di follow-up sia statisticamente significativa (p<0.05).

E.2.2

Secondary objectives of the trial

Secondary Objective: Assess whether Apixaban positively modify microRNA involved in platelet function as compared to Warfarin

stabilire se Apixaban sia in grado di modulare positivamente i microRNAs coinvolti nella funzione piastrinica rispetto al Warfarin.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Men and post-menopause women of age 45 to 80 years with AF who need anticoagulation treatment.No contraindications to Apixaban and Warfarin as per registration. Presence of ischemic heart disease or diabetes (type II). Ability to understand and sign the informed consent.

- Uomini e donne in età post-menopausale (età compresa tra 45 e 80 anni), con storia di cardiopatia ischemica e/o DM tipo 2 (T2DM) senza controindicazioni ad assumere Apixaban e Warfarin, che richiedano terapia anticoagulante orale.

E.4

Principal exclusion criteria

Any acute or chronic condition (infections, cancer, chronic inflammatory diseases) that may interfere with microRNA assessment. Because of the policy of our Ethic Committee on Women of childbearing potential,no women of child bearing potential will be enrolled. • Malignant hypertension - • Patients without supervision and/or at high risk of low compliance to treatment.

- Qualunque condizione acuta o cronica (infezioni, neoplasia, malattia infiammatoria cronica) che possa interferire con la valutazione dei microRNAs.
- Donne in potenziale stato di gravidanza. ipertensione maligna. Pazienti non complianti al trattamento

E.5 End points

E.5.1

Primary end point(s)

differences of the top three differentially expressed microRNA involved in coagulation between patients randomized to Apixaban and Warfarin

Differenza tra I 3 microRNA coinvolti nella coagulazione maggiormente espresso nei due gruppi .

E.5.1.1

Timepoint(s) of evaluation of this end point

3-month

3 mesi

E.5.2

Secondary end point(s)

Lack of thrombo-embolic events

mancanza di eventi tromboembolici

E.5.2.1

Timepoint(s) of evaluation of this end point

3 mounth

3 mesi

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

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

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)

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

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

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)

clinical practice. At the end of the study, a clinical reassessment of randomized patients will be done in order to evaluate the need to continue anticoagulant treatment.

normale pratica clinica che prevede la rivalutazione per il proseguimento della terapia anticoagulante.

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

2016-07-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-21

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

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