Clinical Trials Register

Summary
EudraCT Number:	2011-005047-27
Sponsor's Protocol Code Number:	CIB-ROF-2011-01
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:	2011-11-30
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

2011-005047-27

A.3

Full title of the trial

Estudio clínico aleatorizado, doble-ciego, controlado con placebo, para evaluar el efecto sobre la función endotelial de Roflumilast en pacientes con enfermedad pulmonar obstructiva crónica

A.3.1

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

Estudio clínico aleatorizado, doble-ciego, controlado con placebo, para evaluar el efecto sobre la función endotelial de Roflumilast en pacientes con enfermedad pulmonar obstructiva crónica

A.3.2

Name or abbreviated title of the trial where available

REVASC

A.4.1

Sponsor's protocol code number

CIB-ROF-2011-01

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	CIBERES (Centro de Investigación Biomédica en Red Enfermedades Respiratorias)
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	Nycomed Pharma S.A.
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	CAIBER
B.5.2	Functional name of contact point	CAIBER
B.5.3	Address:
B.5.3.1	Street Address	C/ Melchor Fernández Almagro nº 3. Pabellón 13 - Planta 1.
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28029
B.5.3.4	Country	Spain
B.5.4	Telephone number	0091822 24 94
B.5.5	Fax number	0091387 75 51
B.5.6	E-mail	ugoicoechea@caiber.net

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	Daxas
D.2.1.1.2	Name of the Marketing Authorisation holder	Nycomed GmbH
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	Roflumilast
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	ROFLUMILAST
D.3.9.1	CAS number	162401-32-3
D.3.9.4	EV Substance Code	SUB10358MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	Tablet
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

Pacientes con enfermedad pulmonar obstructiva crónica (EPOC)

E.1.1.1

Medical condition in easily understood language

Pacientes con enfermedad pulmonar obstructiva crónica (EPOC)

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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

Evaluar los efectos de Roflumilast sobre la función endotelial

E.2.2

Secondary objectives of the trial

-Evaluar los efectos de Roflumilast sobre la rigidez arterial.
-Evaluar los efectos de Roflumilast sobre marcadores sistémicos de inflamación, estrés oxidativo y disfunción endotelial.
-Investigar la relación entre la disfunción endotelial, la inflamación sistémica, el estrés oxidativo y la rigidez arterial en pacientes con EPOC

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

?• • Firma del Consentimiento Informado antes de la realización de cualquier procedimiento del estudio
• Edad entre 55 y 75 años
• Fumadores actuales o exfumadores, con historia tabáquica de al menos 20 paquetes/año (exfumadores que hayan abandonado el tabaquismo hace más de un año)
• Diagnóstico de EPOC (criterios GOLD) al menos 1 año antes a la visita basal
• Presencia de bronquitis crónica (tos y/o expectoración durante más de 3 meses al año, durante más de 2 años consecutivos, en ausencia de otra causa potencial)
• Espirometría con FEV1 postbroncodilatador ≤70% teórico
• Presencia de enfermedad cardiovascular establecida o enfermedad cardiovascular equivalente
• Presencia de inflamación sistémica crónica (PCR sérica ≥ 2 mg/L y <10 mg/L)

E.4

Principal exclusion criteria

• Episodio de exacerbación y/o cambios en el tratamiento de la EPOC durante los últimos 2 meses previos a la visita basal
• Historia de asma, lesiones pulmonares residuales o bronquiectasias radiológicamente evidentes
• Síndrome de Apnea-Hipopnea durante el sueño
• Mal control de las ECV y/o cambios en su tratamiento durante los 3 meses previos a la visita basal.
• Arritmias cardíacas hemodinámicamente significativas o deformaciones de válvula cardíaca
• Enfermedades concomitantes graves de tipo inmunológico, inflamatorio, infeccioso o neoplásico
• Insuficiencia hepática moderada o grave (clase B o C según la escala Child-Pugh)
• Desórdenes neurológicos y/o psiquiátricos graves, incluyendo depresión asociada a ideación o comportamiento suicida
• Abuso de alcohol y/o drogas durante los 12 meses previos a la visita basal
• Hipersensibilidad a roflumilast o a alguno de sus excipientes
• Embarazo o embarazo potencial
• Participación en otro ensayo clínico en los 30 días previos a la visita basal
• Dificultades de lenguaje para seguir las instrucciones del estudio
• Toma previa de roflumilast para el tratamiento crónico de la EPOC

E.5 End points

E.5.1

Primary end point(s)

Evolución de la función endotelial utilizando para ello la medida basal y final de la reactividad endotelial mediante tonometría arterial periférica reactiva a la hiperemia.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 semanas

E.5.2

Secondary end point(s)

-Rigidez arterial
-Marcadores de inflamación en sangre: PCR, IL-8, IL-6, IL-10, TNF?, sICAM-1, MCP-1, PARC/CCL-18
-Marcadores de estrés oxidativo: MPO, TRX
-Marcadores de disfunción endotelial: TWEAKs, FasL, ADMA
-Función pulmonar (FEV1, FVC)

E.5.2.1

Timepoint(s) of evaluation of this end point

12 semanas

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

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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

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

Última visita del último paciente

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:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

150

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

150

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)

Not applicable

No aplica

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-01-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-13

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

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