Clinical Trials Register

Summary
EudraCT Number:	2012-000255-13
Sponsor's Protocol Code Number:	11-019
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:	2012-07-23
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-000255-13

A.3

Full title of the trial

Multicenter, Randomized, Active-Controlled Efficacy And Safety Study Comparing Extended Duration Betrixaban With Standard Of Care Enoxaparin For The Prevention Of Venous Thromboembolism In Acute Medically Ill Patients.

Studio multicentrico, randomizzato, controllato con farmaco attivo, sull'efficacia e la sicurezza dell'assunzione prolungata di Betrixaban a confronto con la terapia standard con Enoxaparina nella prevenzione del tromboembolismo venoso in pazienti affetti da patologia medica acuta.

A.3.1

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

A worldwide study comparing the safety and effectiveness of the extended use of the study drug betrixaban against a standard treatment drug, enoxaparin, in patients unexpectedly hospitalised and at risk of developing blood clots.

Studio internazionale per confrontare la sicurezza e l'efficacia dell'uso esteso del farmaco sperimentale betrixaban con la terapia standard, enoxaparina, in pazienti inaspettatamente ospedalizzati a rischio di sviluppare coaguli di sangue.

A.4.1

Sponsor's protocol code number

11-019

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	PORTOLA PHARMACEUTICALS, INC.
B.1.3.4	Country	United States
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	Portola Pharmaceuticals, Inc.
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	Portola Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Janice Castillo (VP Reg Affairs)
B.5.3	Address:
B.5.3.1	Street Address	270 East Grand Avenue
B.5.3.2	Town/ city	South San Francisco
B.5.3.3	Post code	CA 94080
B.5.3.4	Country	United States
B.5.4	Telephone number	001 650-246-7360
B.5.5	Fax number	001 650-246-7376
B.5.6	E-mail	jcastillo@portola.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	Betrixaban Maleate
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Capsule
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	Betrixaban maleate
D.3.9.1	CAS number	330942-05-7
D.3.9.2	Current sponsor code	PRT054021 maleate
D.3.9.3	Other descriptive name	MK4448
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	80
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	Betrixaban Maleate
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Capsule
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	Betrixaban maleate
D.3.9.1	CAS number	330942-05-7
D.3.9.2	Current sponsor code	PRT054021 maleate
D.3.9.3	Other descriptive name	MK4448
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	40
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	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	Lovenox 20mg/0.2 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Aventis
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ENOXAPARIN SODIUM
D.3.9.1	CAS number	9041-08-1
D.3.9.4	EV Substance Code	SUB11933MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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.IMP: 4
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	Clexane 20 mg/0.2 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Aventis
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ENOXAPARIN SODIUM
D.3.9.1	CAS number	9041-08-1
D.3.9.4	EV Substance Code	SUB11933MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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.IMP: 5
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	Lovenox 40 mg / 0.4 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Aventis
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ENOXAPARIN SODIUM
D.3.9.1	CAS number	9041-08-1
D.3.9.4	EV Substance Code	SUB11933MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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.IMP: 6
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	Clexane 40 mg / 0.4 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Aventis
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ENOXAPARIN SODIUM
D.3.9.1	CAS number	9041-08-1
D.3.9.4	EV Substance Code	SUB11933MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 4
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

Prophylaxis of venous thromboembolism.

Profilassi del tromboembolismo venoso

E.1.1.1

Medical condition in easily understood language

Prevention of blood clots

Prevenzione della formazione di coaguli di sangue.

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10049909
E.1.2	Term	Venous thromboembolism 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

Demonstrate the superiority of extended duration (35 days + 7 day window, i.e. 35-42 days allowed) anticoagulation with betrixaban as compared to the standard of care (10 ± 4 days) with enoxaparin for prevention of VTE in patients who are at risk due to acute medical illness.

Dimostrare la superiorita' dell’anticoagulazione di durata estesa (35 giorni + finestra di 7 giorni, ossia sono ammessi 35-42 giorni) con betrixaban rispetto allo standard di cura (10 ± 4 giorni) con enoxaparina nella prevenzione del TEV in pazienti a rischio a causa di patologia medica acuta.

E.2.2

Secondary objectives of the trial

None.

Nessuno.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male or female (non-pregnant, non-breastfeeding women) ages 40 years and older anticipated to be severely immobilized for at least 24 hours after randomization hospitalized with one of the following: o congestive heart failure, o acute respiratory failure, o acute infection without septic shock, o acute rheumatic disorders, o acute ischemic stroke with lower extremity hemiparesis or hemiparalysis.

Uomini o donne (non in gravidanza o allattamento) di eta' superiore o uguale ai 40 anni, avvisati che saranno fortemente immobilizzati per almeno 24 ore dopo la randomizzazione, ospedalizzati per una delle seguenti condizioni: o Insufficienza cardiaca; o Insufficienza respiratoria acuta; o Infezione acuta senza shock settico; o Disturbi reumatici acuti; o Ictus ischemico acuto con emiparesi degli arti inferiori o emi-paralisi.

E.4

Principal exclusion criteria

o A condition requiring prolonged anticoagulation or anti-platelets; o Active bleeding or at high risk of bleeding; o Unable to take oral medication; o ontraindication to anticoagulant therapy; o General conditions in which subjects are not suitable to participate in the study.

o Condizioni che richiedono prolungata terapia anticoagulante o antipiastrinica. o Sanguinamento attivo o rischio di sanguinamento. o Incapacita' di assumere farmaci per via orale. o Controindicazioni alla terapia anticoagulante. o Condizioni generali per le quali il soggetto non e' in grado di partecipare allo studio.

E.5 End points

E.5.1

Primary end point(s)

Efficacy: The primary (composite) outcome is the occurrence of any of the following events through the Day 35 visit: Asymptomatic proximal DVT (as detected by ultrasound), symptomatic DVT (proximal or distal), non-fatal PE, or VTE related death Safety: The primary safety outcome will be the occurrence of major bleeding through 7 days after discontinuation of all study medication.

EFFICACIA L’outcome primario (composito) e' l’occorrenza di uno qualsiasi dei seguenti eventi fino alla visita del Giorno 35: TVP prossimale asintomatica (rilevata con ecografia), TVP sintomatica (prossimale o distale), EP non fatale o decesso legato a TEV. SICUREZZA L’outcome di sicurezza primario sara' l’occorrenza di sanguinamento maggiore fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio.

E.5.1.1

Timepoint(s) of evaluation of this end point

There will be a single interim efficacy and futility analysis of the primary and secondary outcomes when approximately 50% of the primary-endpoint evaluable patients have data (i.e., 2568 patients with an evaluable primary outcome). Efficacy and safety outcomes will be reviewed by the IDMC at the following defined intervals: • After 250 patients have completed follow-up • After 750 patients have completed follow-up • After 1500 patients have completed follow-up • After 3000 patients have completed follow-up • After 4500 patients have completed follow-up • After 2568 patients have evaluable primary outcome data. This may occur simultaneously with one of the above meetings if the meeting criteria coincide.

Sara' effettuata una sola analisi ad interim di efficacia e futilita' degli outcome primari e secondari quando sara' disponibile circa il 50% dei pazienti valutabili per l’endpoint primario (vale a dire 2568 pazienti con un outcome primario valutabile). Gli outcome di efficacia e sicurezza saranno esaminati dal IDMC ai seguenti intervalli definiti: -Dopo che 250 pazienti avranno completato il follow-up (f-up),-Dopo che 750 pazienti avranno completato il f-up, -Dopo che 1500 pazienti avranno completato il f-up, -Dopo che 3000 pazienti avranno completato il f-up, -Dopo che 4500 pazienti avranno completato il f-up, -Dopo che 2568 pazienti disporranno di dati per l’outcome primario valutabile. Cio' potra' anche verificarsi in contemporanea ad uno dei sopra menzionati incontri.

E.5.2

Secondary end point(s)

Efficacy: The key secondary (composite) outcome is the occurrence of any of the following events through the end of the parenteral treatment period: Asymptomatic proximal DVT (as detected by ultrasound), symptomatic DVT (proximal or distal), non-fatal PE, or VTE related death Other Secondary Efficacy Outcomes: The following other secondary composite outcomes will be examined: • Symptomatic VTE: The occurrence of symptomatic VTE through the Day 35 visit (VTE-related death, nonfatal PE or symptomatic DVT). • The occurrence of asymptomatic proximal DVT, symptomatic DVT (proximal or distal), non-fatal PE, or allcause mortality through the Day 35 visit. Safety: Secondary safety outcomes include the following: • Occurrence of clinically relevant non-major bleeding (CRNM bleeding) through 7 days after discontinuation of all study medication. • Occurrence of major bleeding through the time of parenteral study medication discontinuation. • Occurrence of CRNM bleeding through the time of parenteral study medication discontinuation. • Occurrence of major bleeding from the time of parenteral study medication discontinuation through Day 35. • Occurrence of CRNM bleeding from the time of parenteral study medication discontinuation through Day 35. • Occurrence of major bleeding through the time of parenteral study medication discontinuation in patientswith severe renal insufficiency (creatinine clearance < 30 ml/min). • Occurrence of CRNM bleeding through the time of parenteral study medication discontinuation in patients with severe renal insufficiency. • Occurrence of major bleeding through 7 days after discontinuation of all study medication in patients with severe renal insufficiency. • Occurrence of CRNM bleeding through 7 days after discontinuation of all study medication in patients with severe renal insufficiency. • Occurrence of stroke, as adjudicated by the CEC.

EFFICACIA L’outcome chiave secondario (composito) e' l’occorrenza di uno qualsiasi dei seguenti eventi fino alla fine del trattamento parenterale: TVP prossimale asintomatica (rilevata con ecografia), TVP sintomatica (prossimale o distale), EP non fatale o decesso legato a TEV. Altri parametri secondari di efficacia: • TEV sintomatico: L’occorrenza di TEV sintomatico fino alla visita del Giorno 35 (decesso legato a TEV, EP non fatale o TVP sintomatica) • L’occorrenza di TVP prossimale asintomatica, TVP sintomatica (prossimale o distale), EP non fatale o mortalita' per tutte le cause fino alla visita del Giorno 35 SICUREZZA • L’occorrenza di sanguinamento non maggiore clinicamente rilevante (sanguinamento CRNM) fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio • Occorrenza di sanguinamento maggiore fino al momento dell’interruzione del farmaco dello studio per via parenterale • Occorrenza di sanguinamento CRNM fino al momento dell’interruzione del farmaco dello studio per via parenterale • Occorrenza di sanguinamento maggiore dal momento dell’interruzione del farmaco dello studio per via parenterale fino al Giorno 35 • Occorrenza di sanguinamento CRNM dal momento dell’interruzione del farmaco dello studio per via parenterale fino al Giorno 35 • Occorrenza di sanguinamento maggiore fino al momento dell’interruzione del farmaco dello studio per via parenterale in pazienti con insufficienza renale grave (clearance della creatinina < 30 ml/min) • Occorrenza di sanguinamento CRNM fino al momento dell’interruzione del farmaco dello studio per via parenterale in pazienti con insufficienza renale grave • Occorrenza di sanguinamento maggiore fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio in pazienti con insufficienza renale grave • Occorrenza di sanguinamento CRNM fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio in pazienti con insufficienza renale grave • Occorrenza di ictus, stabilito dal CEC.

E.5.2.1

Timepoint(s) of evaluation of this end point

Sara' effettuata una sola analisi ad interim di efficacia e futilita' degli outcome primari e secondari quando sara' disponibile circa il 50% dei pazienti valutabili per l’endpoint primario (vale a dire 2568 pazienti con un outcome primario valutabile). Gli outcome di efficacia e sicurezza saranno esaminati dall’IDMC ai seguenti intervalli definiti: -Dopo che 250 pazienti avranno completato il follow-up (f-up),-Dopo che 750 pazienti avranno completato il f-up, -Dopo che 1500 pazienti avranno completato il f-up, -Dopo che 3000 pazienti avranno completato il f-up, -Dopo che 4500 pazienti avranno completato il f-up, -Dopo che 2568 pazienti disporranno di dati per l’outcome primario valutabile. Cio' potra' anche verificarsi in contemporanea ad uno dei sopra menzionati incontri.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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)

Yes

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

doppio mascheramento

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

136

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

Brazil

Canada

Chile

Croatia

Hong Kong

India

Israel

Korea, Republic of

Mexico

Peru

Russian Federation

Singapore

South Africa

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

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

Number of subjects for this age range:

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:

2000

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

4850

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

4047

F.4.2.2

In the whole clinical trial

6850

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

Nessuno

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

2012-08-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-01-25

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials