Clinical Trials Register

Summary
EudraCT Number:	2010-024657-36
Sponsor's Protocol Code Number:	DSR-01
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-15
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

Denmark - DHMA

A.2

EudraCT number

2010-024657-36

A.3

Full title of the trial

Metronidazol for the treatment of dientamoebiasis in children in Denmark – A randomized, placebo-controlled, double-blinded clinical trial.

A.3.1

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

A study into the effect of metronidazole treatment on infection with Dientamoeba fragilis in children in Denmark.

A.3.2

Name or abbreviated title of the trial where available

DFPT

A.4.1

Sponsor's protocol code number

DSR-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	Statens Serum Institut
B.1.3.4	Country	Denmark
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	Statens Serum Institut
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Statens Serum Institut
B.5.2	Functional name of contact point	DFPT Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Artillerivej 5
B.5.3.2	Town/ city	Copenhagen
B.5.3.3	Post code	2300
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4532683604
B.5.5	Fax number	+4532683862
B.5.6	E-mail	dsr@ssi.dk

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	Flagyl® (Metronidazole), oral suspension. Sanofi-aventis
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Denmark A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Metronidazol
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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	Matronidazole
D.3.9.1	CAS number	13182893
D.3.9.2	Current sponsor code	DSR-01
D.3.9.3	Other descriptive name	METRONIDAZOLE BENZOATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	Yes
D.3.11.13.1	Other medicinal product type	Antibiotic

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	Oral suspension
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

Presumed symptomatic gastrointestinal infection with the protozoan Dientamoeba fragilis.

E.1.1.1

Medical condition in easily understood language

An infection in the gut with a small single-celled organism called Dientamoeba fragilis, which is suspected of causing illness in children and adults.

E.1.1.2

Therapeutic area

Diseases [C] - Parasitic Diseases [C03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10006051
E.1.2	Term	Bowel dysfunction
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10016766
E.1.2	Term	Flatulence
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10021907
E.1.2	Term	Infectious diarrhea
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10034453
E.1.2	Term	Perianal itching
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10017999
E.1.2	Term	Gastrointestinal pain
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10016165
E.1.2	Term	Failure to thrive
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10067720
E.1.2	Term	Parasitic gastroenteritis
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

To answer the following:
What is the effect of metronidazole in children with gastrointestinal complaints and proven D. fragilis-infection, in which no other aetiology is known and no other intestinal pathogens could be shown?

E.2.2

Secondary objectives of the trial

To answer the following:
What is the effect of metronidazole on eradicating D. fragilis?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients with samples investigated at Statens Serum Institut.
• Faecal sample (index) positive for Dientamoeba fragilis (DF) by realtime PCR, within <7 days.
• No faecal samples positive for DF within the period: 3 months prior to and up to index-sample.
• Telephone interview to parents no later then 14 days after result from index-sample.
• Age 3-12 years.
• Place of residence: Island of Zealand, incl. capital region.
• Symptoms consistent with gastrointestinal infection of DF: Either 1) ≥2 episodes of diarrhea per week or 2) ≥2 episodes of stomach ache per week or 3) ≥2 of the following symptoms: Anorexia, Failure to thrive, Anal itching, excessive flatulence, other change in bowel movements.

E.4

Principal exclusion criteria

• Expected non-compliance.
• Objection to subject participation from referring physician.
• Underlying illness or comorbidity, incl. known gastrointestinal illness (both infectious and non-infectious), but excluding constipation.
• Known liver disease or intolerance/allergy to metronidazole.
• Positive screening for other intestinal pathogens, which may explain subject symptoms.
• Treatment with metronidazole outside of study within study period.
• Weight > 50 kg

E.5 End points

E.5.1

Primary end point(s)

In children with gastrointestinal (GI) complaints and a GI-infection with D. fragilis, where no other aetiology is known and no other intestinal pathogens have been shown, what is the effect of metronidazol on the level of symptoms?

Primary endpoint: Clinical improvement in overall GI-symptomatology.

Measurement device: Visual-Analog-Scale (VAS).

Comments: End point aims to show a drop, when comparing pre-treatment to post-treatment level. A significant difference in drop between subjects treated with metronidazole and subjects treated with placebo, will be taken into account as effect of metronidazole on symptoms.

Statistics: Analysis of varians, subsidiary a non-parametric method if data can not be viewed as normally distributed.

E.5.1.1

Timepoint(s) of evaluation of this end point

14 days after end of treatment period

E.5.2

Secondary end point(s)

Secondary end point will be registered using a specific realtime PCR for D. fragilis, performed on faecal samples collected from study-participant.

Results will be noted as either positive or negative.

E.5.2.1

Timepoint(s) of evaluation of this end point

Sample collection 14 days after end of treatment period

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

End of trial: Upon inclusion and completion of 100 subjects. Anticipated for May 2013.

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

Yes

F.1.1