Clinical Trials Register

Summary
EudraCT Number:	2013-004619-31
Sponsor's Protocol Code Number:	2819-MA-1002
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-02-05
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2013-004619-31

A.3

Full title of the trial

A phase IIIb/IV randomized, controlled, open label, parallel group study to compare the efficacy of vancomycin therapy to extended duration fidaxomicin therapy in the sustained clinical cure of Clostridium difficile Infection in an older population

A.3.1

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

A study in which two antibiotics (vancomycin and fidaxomicin) are compared in older patients with infections of the gut caused by bacteria called Clostridium difficile.

A.3.2

Name or abbreviated title of the trial where available

EXTEND

A.4.1

Sponsor's protocol code number

2819-MA-1002

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	Andreas Karas
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.5.6	E-mail	andreas.karas@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 B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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 200 mg film-coated tablets
D.3.4	Pharmaceutical form	Film-coated 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	fidaxomicin
D.3.9.1	CAS number	873857-62-6
D.3.9.2	Current sponsor code	OPT-80
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	Vancomycin Capsules 125 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	Xellia Pharmaceutica ApS. (formerly Alpharma ApS)
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	Vancomycin Capsules 125 MG
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	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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Clostridium Difficile Infection (CDI) also known as C. difficile-associated diarrhoea (CDAD)

E.1.1.1

Medical condition in easily understood language

Infection of the gut caused by bacteria called Clostridium difficile

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	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10022661
E.1.2	Term	Intestinal infection due to clostridium difficile
E.1.2	System Organ Class	100000004862

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 evaluate whether the extended duration fidaxomicin therapy is superior to the standard vancomycin therapy in sustained clinical cure of CDI at 30 days after end of treatment (Day 40 or Day 55). Sustained clinical cure is defined as clinical response at Test of Cure (TOC) and no recurrence of CDI from TOC until time of assessment.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
• to compare sustained clinical cure of CDI at Day 40, Day 55 and Day 90
• to compare clinical response of CDI at 2 days after end of treatment (Day 12 or Day 27)
• to compare clinical response of CDI at Day 12
• to compare TTROD in hours
• to compare recurrence rate of CDI at Day 40, Day 55 and Day 90
• to compare time to recurrence after end of treatment
• to compare disease-free survival after Day 10
• to compare the rate of relapse at Day 90 as determined by whole genome sequencing of C.Difficile isolates from subjects who have documented recurrence after TOC
• to compare incidence of mortality and severity of adverse events at Day 90
• to assess change in Health Related Quality of Life from baseline to Day 12, Day 27, Day 40, Day 55 and recurrence using the EQ-5D-5L questionnaire
• to compare readmissions and length of hospital stay at Day 90

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

There are two sub-studies:
• Pharmacokinetic (Blood) Analysis Sub-Study involving approximately 10 patients, and
• Stool Microbiome & Fecal Fidaxomicin Concentration Analysis Sub-Study involving approximately 80 patients

The sub-study objectives are as follows
• To assess plasma and stool levels of fidaxomicin with extended dose regimen
• To assess the comparative impact of fidaxomicin versus vancomycin on the microbiome and the lifecycle of C. difficile

E.3

Principal inclusion criteria

• Subject is 60 years of age or over.
• CDI is confirmed by clinical symptoms in the 24 hours prior to randomization and CDI test confirmed positive for presence of C. difficile toxin A or B in stool within 48 hr prior to randomization.
• Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
• Subject agrees not to participate in another interventional study whilst participating in this study.

E.4

Principal exclusion criteria

• Subject is taking or requiring to be treated with prohibited medications
• Subject has received more than one day of dosing of any therapy for CDI within the last 48 hours
• Subject has experienced more than 2 previous episodes of CDI in the 3 months prior to study enrolment
• Subject is unable to swallow oral study medication.
• Subject has a current diagnosis of toxic megacolon.
• Subject is not willing to adhere to the provisions of treatment and observation specified in the protocol.
• Subject has been randomized into this study previously, has taken any investigational drug within 28 days or 5 half lives, whichever is longer, 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.
• Subject has previously participated in a CDI vaccine study
• Subject has hypersensitivity to fidaxomicin, vancomycin or any of its components.
• Any clinical condition which, in the opinion of the Investigator, would not allow safe completion of this study.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this study is sustained clinical cure of CDI

E.5.1.1

Timepoint(s) of evaluation of this end point

30 days after end of treatment (Day 40 or Day 55)

E.5.2

Secondary end point(s)

• Sustained clinical cure of CDI at Day 40, Day 55 and Day 90
• Clinical response of CDI at 2 days after EOT (Day 12 or Day 27)
• Clinical response of CDI at Day 12
• TTROD in hours
• Recurrence rate of CDI at Day 40, Day 55 and Day 90
• Time to recurrence after end of treatment (only for subjects with clinical response)
• Disease-free survival after Day 10 (only for subjects with clinical response)
• Rate of relapse at Day 90 as determined by whole genome sequencing of C.difficile isolates from Subjects who have documented recurrence after TOC

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 12, 27, 40 , 55, 90 depending on treatment and endpoint

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

130

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

Austria

Belgium

Croatia

Czech Republic

Denmark

Finland

France

Germany

Greece

Hungary

Ireland

Italy

Norway

Poland

Portugal

Romania

Russian Federation

Slovenia

Spain

Sweden

Switzerland

Turkey

United Kingdom

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.1.1.1

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

300

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

322

F.4.2.2

In the whole clinical trial

364

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
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

2015-03-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-05-05

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