Clinical Trials Register

Summary
EudraCT Number:	2012-000531-88
Sponsor's Protocol Code Number:	FID-EC-0001
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:	2013-01-23
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2012-000531-88

A.3

Full title of the trial

A Phase IIIb/IV Randomized, Controlled, Double-blind, Double-dummy, Parallel Group Study to Compare the Efficacy of Fidaxomicin to Vancomycin in the Sustained Clinical Cure of Clostridium Difficile Infection in Adults Receiving Immunosuppressive Therapy.

Estudio en fase IIIb/IV, aleatorizado, controlado, doble-ciego, con doble-enmascaramiento y de grupos paralelos, para comparar la eficacia de Fidaxomicina frente a Vancomicina en relación con la curación clínica sostenida de la infección por Clostridium Difficile en adultos que reciben terapia inmunosupresora

A.3.1

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

This clinical study investigates the effect of fidaxomicin in comparison to vancomycin in adult patients with an infection of Clostridium difficile, and are using medicinal products that suppress the immune system.

Este estudio clínico investiga los efectos de Fidaxomicina frente a Vancomicina en pacientes adultos que tienen una infección de Clostridium difficile y que reciben terapia inmunosupresora

A.3.2

Name or abbreviated title of the trial where available

Freedom Study

Estudio Freedom

A.4.1

Sponsor's protocol code number

FID-EC-0001

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	Astellas Pharma Europe Ltd.
B.1.3.4	Country	United Kingdom
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	Astellas Pharma Europe Ltd.
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Astellas Pharma Europe Ltd.
B.5.2	Functional name of contact point	Gemma Waygood
B.5.3	Address:
B.5.3.1	Street Address	2000 Hillswood Drive
B.5.3.2	Town/ city	Chertsey
B.5.3.3	Post code	KT16 0RS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	441784415512
B.5.6	E-mail	gemma.waygood@astellas.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	Dificlir
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma Europe BV
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	Dificlir (fidaxamicin)
D.3.4	Pharmaceutical form	Capsule, hard
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	fidaxomicin
D.3.9.1	CAS number	873857-62-6
D.3.9.3	Other descriptive name	FIDAXOMICIN
D.3.9.4	EV Substance Code	SUB31455
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	200
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	Vancocin
D.2.1.1.2	Name of the Marketing Authorisation holder	Flynn Pharma Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Vancocin
D.3.4	Pharmaceutical form	Capsule, hard
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	VANCOMYCIN
D.3.9.1	CAS number	1404-90-6
D.3.9.3	Other descriptive name	Vancocin
D.3.9.4	EV Substance Code	SUB05076MIG
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	125
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	Capsule, hard
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

Adult patients with Clostridium difficile infection who are receiving immunosuppressive therapy.

Pacientes adultos con infeccion Clostridium difficile y están recibiendo terapia inmunosupresora

E.1.1.1

Medical condition in easily understood language

Adult patients with an infection of Clostridium difficile who are using medicinal products that suppress the immune system.

Pacientes adultos con infeccion de Clostridium difficile que estan usando productos medicinales que deprimen el sistema inmune

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

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	10061043
E.1.2	Term	Clostridial infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to demonstrate superiority of fidaxomicin versus vancomycin for the sustained clinical cure of Clostridium difficile Infection (CDI) in adult patients receiving immunosuppressive therapy. Sustained clinical cure is defined as clinical cure without recurrence within 14 days from Test of Cure (TOC).

El objetivo principal del estudio es demostrar la superioridad de fidaxomicina frente a vancomicina en relación con la curación clínica sostenida de la infección por Clostridium difficile (ICD) en pacientes adultos que reciben terapia inmunosupresora.La curación clínica sostenida se define como la curación clínica sin recurrencia en los 14 días siguientes a la prueba de curación (TOC).

E.2.2

Secondary objectives of the trial

not applicable

No procede

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A subject is eligible for the study if all of the following apply:
1. Subject is 18 years of age or over.
2. CDI is confirmed by clinical symptoms (see Section 5.2.3) and rapid CDI test (see Section 5.7)
3. Subject has not been treated with medication or other therapy for CDI within the last 10 days.
4. Subject is:
? receiving immunosuppressive therapy (chemotherapy) or is undergoing a stem cell transplant procedure (defined as the time period from the start of conditioning prior to transplant until 6 months after infusion of stem cells) for a hematological malignancy; or
? receiving immunosuppressive therapy (chemotherapy) for a solid tumor malignancy or following solid organ transplantation; or
? being treated with immunosuppressive and /or anti-TNF therapy for an auto-immune disease
5. Subject has signed written informed consent.
6. Any woman of childbearing potential requires negative serum or urine pregnancy test before entry to the study.
7. Male and female subjects that are sexually active must agree to practice effective birth control during the study and for 30 days after the end of the study. (An effective method of birth control is defined as those which result in a low failure rate (CPMP/ICH/286/95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner).

1. Pacientes ?18 años de edad.
2. Confirmación de la ICD por los síntomas clínicos (véase la Sección 5.2.3) y prueba rápida ICD (véase la Sección 5.7).
3. Pacientes que no hayan recibido medicación u otro tratamiento para la ICD en los últimos 10 días.
4. Pacientes que:
? estén recibiendo terapia inmunosupresora (quimioterapia) o en proceso de recibir un trasplante de células madre (definido como el periodo de tiempo entre el inicio del acondicionamiento previo al trasplante y 6 meses después de la infusión de las células madre) para una neoplasia hematológica; o
? estén recibiendo terapia inmunosupresora (quimioterapia) por un tumor sólido maligno o después de un trasplante de órgano sólido; o
? se estén tratando con terapia inmunosupresora y/o anti-TNF para una enfermedad auto-inmune.
5. Pacientes que hayan firmado el consentimiento informado por escrito.
6. Cualquier mujer en edad fértil debe hacerse una prueba de embarazo en suero u orina antes de su inclusión en el estudio.
7. Los hombres y mujeres sexualmente activos deberán utilizar métodos anticonceptivos eficaces durante el estudio y los 30 días siguientes al final del estudio. Se define como método anticonceptivo eficaz aquel que asocia una tasa de fracaso baja (CPMP/ICH/286/95 modificado), de menos del 1% al año, cuando se utiliza de forma constante y correcta, como pueden ser los implantes, los inyectables, los anticonceptivos orales combinados, algunos dispositivos intrauterinos (DIU), la abstinencia sexual o la pareja vasectomizada.

E.4

Principal exclusion criteria

Subject will be excluded from participation in this study if any of the following apply:
1. The subject has experienced more than one episode of CDI within the 3 months prior to study inclusion.
2. Taking or requiring to be treated with prohibited medications listed in Section 5.1.3.2.
3. Unable to take oral study medication.
4. Female patients that are pregnant, intend to become pregnant or are breastfeeding.
5. History of ulcerative colitis or Crohn?s disease.
6. History or diagnosis of toxic megacolon or pseudomembranous colitis.
7. Not willing to adhere to the provisions of treatment and procedures specified in the protocol.
8. Has taken an investigational drug within 28 days prior to enrollment, or is currently participating in another clinical study which may influence the assessment of efficacy and/or safety endpoints of this study, in the opinion of the Sponsor.
9. Hypersensitivity to fidaxomicin or any of its components.
10. Hypersensitivity to vancomycin or any of its components.
11. Any clinical condition which, in the opinion of the investigator, would not allow safe completion of this study.

1. Pacientes con más de un episodio previo de ICD en los 3 meses previos a la inclusión en el estudio.
2. Pacientes que reciben o necesitan recibir tratamiento con alguno de los medicamentos prohibidos incluidos en la Sección 5.1.3.2.
3. Pacientes incapaces de tomar la medicación del estudio por vía oral.
4. Pacientes embarazadas, que estén intentando quedarse embarazadas o en periodo de lactancia.
5. Historial de enfermedad de Crohn o colitis ulcerosa.
6. Historial o diagnóstico de megacolon tóxico o colitis pseudomembranosa.
7. Pacientes que no están dispuestos a seguir el tratamiento y los procedimientos especificados en el protocolo.
8. Pacientes que hayan tomado cualquier fármaco en investigación en los 28 días previos a la inclusión, o que estén participando actualmente en otro estudio clínico que pueda influir en la evaluación de la eficacia y/o seguridad de este estudio, según la opinión del Promotor.
9. Hipersensibilidad a fidaxomicina o a cualquiera de sus componentes.
10. Hipersensibilidad a vancomicina o a cualquiera de sus componentes.
11. Cualquier situación clínica que, en opinión del investigador, no permita la terminación de este estudio en condiciones de seguridad.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint in this study is the rate of sustained clinical cure 14 days after TOC (at Day 26).

La variable principal en este estudio es la curación clínica sostenida 14 dias después del TOC (día 26)

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 26

Dia 26

E.5.2

Secondary end point(s)

not applicable

No procede

E.5.2.1

Timepoint(s) of evaluation of this end point

not applicable

No procede

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

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

Yes

E.8.1.7.1

Other trial design description

doble enmascaramiento

double dummy

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

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

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

Russian Federation

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

visit 4 at day 40

Visita 4, día 40

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:

640

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

512

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

immunocompromised patients

Pacientes inmunocomprometidos

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

610

F.4.2.2

In the whole clinical trial

640

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

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

2012-10-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-05

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

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