Clinical Trials Register

Summary
EudraCT Number:	2012-000531-88
Sponsor's Protocol Code Number:	FID-EC-0001
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:	2012-07-25
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

Italy - Italian Medicines Agency

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.

Studio di fase IIIb/IV randomizzato, controllato, in doppio cieco, double dummy, a gruppi paralleli per confrontare l'efficacia di fidaxomicina vs. vancomicina nella guarigione clinica prolungata da infezioni da Clostridium difficile negli adulti sottoposti a terapia immunosoppressiva.

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.

Questo studio clinico vuole indagare l'effetto della fidaxomicina rispetto alla vancomicina in pazienti adulti con ifeione da Clostridium difficile, e che stanno assumendo farmaci per sopprimere il sistema immunitario.

A.3.2

Name or abbreviated title of the trial where available

FREEDOM study

Studio 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
B.1.3.4	Country	Italy
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	Lovett House, Lovett Road
B.5.3.2	Town/ city	Staines, Middlesex
B.5.3.3	Post code	TW183AZ
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	Netherlands
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	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.3.9.2	Current sponsor code	OPT-80
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.3.4	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.3.9.4	EV Substance Code	SUB05076MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mEq/µl milliequivalent(s)/microlitre
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.

Pazienti adulti con infesione da Clostridium difficile sottoposti a terapia immunosoppressiva

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.

Pazienti adulti con infezione da Clostridium difficile che stanno usando farmaci per sopprimere il sistema immunitario

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).

L’obiettivo primario è quello di dimostrare la superiorità di fidaxomicina vs. vancomicina per la guarigione clinica prolungata dalle infezioni da Clostridium difficile (CDI) negli adulti sottoposti a terapia immunosoppressiva. La guarigione clinica prolungata è definita come cure cliniche senza ricomparsa entro 14 giorni dalla valutazione della guarigione clinica (TOC)

E.2.2

Secondary objectives of the trial

Secondary objectives of this study are
- to compare the rates of clinical cure of CDI at TOC on Day 12 and of sustained clinical cure of CDI at Day 40 after treatment with fidaxomicin or vancomycin
-to compare the recurrence rate of CDI after treatment with fidaxomicin or vancomycin
- to compare the time to resolution of diarrhea on treatment with fidaxomicin or vancomycin

Gli obiettivi secondari di questo studio sono:
-confrontare i tassi di guarigione clinica della CDI al TOC al Giorno 12 e di guarigione clinica prolungata della CDI al TOC al Giorno 40 in seguito a trattamento con fidaxomicina o vancomicina
-confrontare il tasso di recidiva della CDI in seguito a trattamento con fidaxomicina o vancomicina
-confrontare il tempo alla risoluzione della diarrea in concomitanza con il trattamento con fidaxomicina o vancomicina

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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 whenused consistently and correctly such as implants,injectables,
combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner).

1.Il soggetto ha un’età ≥18 anni.
2.La CDI è confermata da sintomi clinici (vedere Sezione 5.2.3) e dal test rapido di infezione da Clostridium difficile (vedere Sezione 5.7).
3.Il soggetto non è stato trattato con un farmaco o altra terapia per la CDI negli ultimi 10 giorni.
4.Il soggetto è sottoposto a:
•terapia immunosoppressiva (chemioterapia) o a una procedura di trapianto di cellule staminali (definita come il periodo dall’inizio del condizionamento precedente al trapianto a 6 mesi dopo l’infusione delle cellule staminali) per una malignità ematologica; o
•terapia immunosoppressiva (chemioterapia) per una malignità da tumore solido o in seguito a trapianto di organo solido; o
•trattamento con una terapia immunosoppressiva e/o una terapia anti-TNF per una malattia autoimmune
5.Il soggetto ha firmato il consenso informato scritto.
6.Qualsiasi donna potenzialmente fertile deve essere stata sottoposta a un test di gravidanza sierologico o urinario negativo prima di essere inclusa nello studio.
7.I soggetti maschili e femminili sessualmente attivi devono essere d’accordo di sottoporsi a un efficace controllo delle nascite durante lo studio e per 30 giorni dopo la conclusione dello stesso. (Un metodo di controllo delle nascite efficace è definito come un metodo associato a un basso tasso di insuccesso (CPMP/ICH/286/95 modificato), inferiore all’1% all’anno con un utilizzo regolare e corretto, per esempio impianti, preparati iniettabili, contraccettivi orali combinati, dispositivi intrauterini (IUD), astinenza sessuale o partner vasectomizzato).

E.4

Principal exclusion criteria

1.The subject has experienced more than one previous 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 observation 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.Il soggetto è stato esposto a più di un episodio di CDI entro i 3 mesi precedenti l’inclusione nello studio.
2.Assunzione o necessità di trattamento con farmaci proibiti di cui alla Sezione 5.1.3.2.
3.Incapacità di assumere il farmaco orale in studio.
4.Pazienti femminili che sono in gravidanza, pianificano una gravidanza o stanno allattando al seno.
5.Storia clinica di colite ulcerosa o morbo di Crohn.
6.Storia clinica o diagnosi di megacolon tossico o colite pseudomembranosa.
7.Mancata disponibilità ad attenersi alle direttive del trattamento e a quanto specificato nel protocollo.
8.Il soggetto ha assunto un farmaco sperimentale entro i 28 giorni precedenti l’arruolamento o sta partecipando a un altro studio clinico che potrebbe influenzare la valutazione dell’efficacia e/o degli endpoint di sicurezza di questo studio, secondo l’opinione dello Sponsor.
9.Ipersensibilità alla fidaxomicina o a uno qualsiasi degli eccipienti.
10.Ipersensibilità alla vancomicina o a uno qualsiasi degli eccipienti.
11.Qualsiasi condizione clinica che, secondo l’opinione dello sperimentatore, non consentirebbe di portare a termine questo studio in modo sicuro.

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)

L’endpoint primario sarà la guarigione clinica prolungata a 14 giorni dopo il TOC (Giorno 26)

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 26

Giorno 26

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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

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

Visita 4 al giorno 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

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:

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

immunocompromized patients

pazienti immunocompromessi

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

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

2012-09-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2013-03-13

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