Clinical Trials Register

Summary
EudraCT Number:	2006-001446-14
Sponsor's Protocol Code Number:	N/GF-TORAFIC-06
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-03-20
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

Spain - AEMPS

A.2

EudraCT number

2006-001446-14

A.3

Full title of the trial

Multicenter parallel-group, concealed and randomized allocation and blinded-endpoint study, to evaluate the effects of Torasemide PR versus furosemide on a biochemical marker of collagen synthesis and deposition, in hypertensive patients with heart failure

Ensayo clínico multicéntrico, paralelo, con asignación oculta y aleatorizada, y evaluación enmascarada, para estudiar los efectos sobre un marcador sérico de síntesis y depósito miocárdico de fibras de colágeno, de torasemida LP versus furosemida en pacientes con insuficiencia cardíaca crónica de origen hipertensivo

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

TORAFIC

A.4.1

Sponsor's protocol code number

N/GF-TORAFIC-06

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	NOVAG S.A., FERRER GRUPO
B.1.3.4	Country	Spain
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	NOVAG S.A., FERRER GRUPO
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	NOVAG S.A., FERRER GRUPO
B.5.2	Functional name of contact point	Medical Advisor, Dpto. Médico
B.5.3	Address:
B.5.3.1	Street Address	GRAN VÍA CARLOS III, 94
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08028
B.5.3.4	Country	Spain
B.5.4	Telephone number	3493600 37 28
B.5.5	Fax number	3493490 70 78
B.5.6	E-mail	efernandez@ferrergrupo.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	SUTRILNEO
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVAG, S.A. FERRER GRUPO
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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	Torasemida
D.3.9.1	CAS number	56211-04-6
D.3.9.2	Current sponsor code	AC4464
D.3.9.3	Other descriptive name	BM02015,JDL464,N-(((metiletil) amino)carbonil)-4-((3-metilfenil)-amino)
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	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	SEGURIL
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI AVENTIS
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	SEGURIL
D.3.2	Product code	NO PROCEDE
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	Furosemida
D.3.9.1	CAS number	C03CA
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.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

Heart failure

Insuficiencia cardíaca

E.1.1.1

Medical condition in easily understood language

Heart failure

Insuficiencia cardíaca

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	10007582
E.1.2	Term	Cardiac insufficiency
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

Demostrar la superioridad de Torasemida-LP respecto Furosemida en la reducción de la fibrosis miocárdica en pacientes con insuficiencia cardíaca, en grados II, III y IV, según clasificación de la New York Heart Association (NYHA).

E.2.2

Secondary objectives of the trial

- Valorar eficacia de Torasemida LP versus furosemida en pacientes con insuficiencia cardíaca mediante la medida de los cambios en los signos y síntomas de la patología en estudio.
- Valorar incidencia de eventos cardiovasculares durante el seguimiento del tratamiento en estudio.
- Valorar incidencia de ingresos hospitalarios y/o atenciones en urgencias (estancias <24 horas) y/o atenciones domiciliarias por causa cardiovascular vinculada a la patología en estudio durante el seguimiento.
- Valorar seguridad y tolerabilidad de Torasemida LP versus furosemida en el tratamiento de la insuficiencia cardíaca.
- Valorar los cambios en la Calidad de Vida (CV) mediante el Test de Minnesota en pacientes con insuficiencia cardiaca que estén recibiendo Torasemida LP versus furosemida.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Edad superior a 18 años.
2. Pacientes con insuficiencia cardiaca grado II, II y IV, según criterios de ESC-2005 (ver anexo VIII), con fracción de eyección del ventrículo izquierdo preservada (FE >40%) o deprimida.
3. Pacientes con IC clínicamente estable (ver criterios en anexo IX), que precisen diuréticos para su tratamiento.
4. Pacientes con hipertrofia ventricular izquierda diagnosticada por ecocardiograma (ver anexo VIII).
5. Pacientes con diagnóstico establecido de hipertensión arterial (ver anexo VII).
6. Pacientes sin cardiopatía isquémica o bien, con antecedentes de cardiopatía isquémica no reciente (infarto de miocardio previo hace más de 6 meses o síndrome coronario, accidente vascular cerebral o vasculopatía periférica acontecido hace más de 3 meses).
7. Pacientes que cuyo estado psíquico, cognitivo y/o clínico no suponga un impedimento para comprender la naturaleza del estudio ni para completar el seguimiento.
8. Pacientes que otorguen su consentimiento por escrito para participar en el estudio

E.4

Principal exclusion criteria

1. Pacientes con diagnóstico de IC cuya etiología sea estenosis aórtica o miocardiopatía hipertrófica.
2. Pacientes con antecedentes recientes de síndrome coronario, accidente vascular cerebral o de vasculopatía periférica, (acontecidos durante los últimos 3 meses).
3. Pacientes con antecedentes recientes de infarto agudo de miocardio (que se produjo en los últimos 6 meses).
4. Pacientes con angina de pecho inestable.
5. Pacientes con arritmia cardiaca severa (taquicardia ventricular mantenida, fibrilación auricular, flutter auricular, bradicardia por debajo de 45 latidos por minuto).
6. Mujeres embarazadas o en periodo de lactancia y mujeres en edad fértil que no estén utilizando un método anticonceptivo seguro o que no tengan intención de utilizarlo durante el desarrollo del ensayo. Se considera un método anticonceptivo seguro, los tratamientos anticonceptivos orales o parenterales, o los métodos de barrera: preservativo masculinos o femeninos, diafragma y/o DIU.
7. Pacientes en tratamiento con fármacos antialdosterónicos, en los 6 meses previos al inicio del ensayo.
8. Pacientes con antecedentes de hipersensibilidad conocida al compuesto en estudio o a las sulfonilureas
9. Pacientes con insuficiencia hepática definida por los siguientes parámetros analíticos: SGPT (ALT) o SGOT (AST) más de dos veces por encima del límite superior de la normalidad.
10. Pacientes con insuficiencia renal crónica definida por los siguientes parámetros analíticos:
Creatinina sérica superior a 2,5 mg/dl
Filtrado glomerular <30%
11. Pacientes con diabetes mellitus insulino-dependiente no controlada
12. Pacientes en los que se detecten contraindicaciones a partir de los datos obtenidos durante la selección en la exploración física, hematología, bioquímica, análisis de orina y ECG de 12 derivaciones
13. Participación simultánea en otro ensayo clínico o tratamiento con cualquier fármaco en fase de investigación dentro de los 30 días previos a la firma del consentimiento informado
14. Pacientes con intolerancia a la lactosa.
15. Pacientes con tratamiento concomitante con litio
16. Pacientes que precisen tratamientos crónicos (tratamiento > a 7 días) con anti-inflamatorios no esteroideos, inclusive aspirina.
17. Pacientes con tratamiento concomitante con antibióticos amino glucósidos, ácido etacrínico.
18. Pacientes en tratamiento con antiarrítmicos del grupo 1a, 1b o 2.
19. Historia de dependencia a drogas o alcohol dentro de los 6 meses previos al inicio del ensayo
20. Cualquier circunstancia o condición clínica que, en opinión del investigador, no permitiría completar con seguridad el protocolo y la administración de Torasemida LP o Furosemida.
21. Pacientes que se encuentren controlados a dosis superiores de torasemida 10mg/día o furosemida 40mg/día o que hayan precisado dosis más altas a las mencionadas para mantener la estabilidad de la insuficiencia cardíaca en el mes anterior al inicio del ensayo.

E.5 End points

E.5.1

Primary end point(s)

Concentraciones séricas del péptido carboxiterminal del procolágeno tipo I (PIP).

E.5.1.1

Timepoint(s) of evaluation of this end point

8 meses

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

8 meses

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

142

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

142

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)

no aplica

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

2006-10-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-09-07

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

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