Clinical Trials Register

Summary
EudraCT Number:	2013-003931-30
Sponsor's Protocol Code Number:	CBS-EAM-10d
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:	2014-01-20
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2013-003931-30

A.3

Full title of the trial

A prospective open-label study on efficacy and tolerability of colloidal bismuth sub-citrate as adjunctive therapy to a combination of esomeprazole, amoxicillin and metronidazole for 10 days for Helicobacter pylori elimination in children.

A.3.1

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

Study on efficacy and tolerabilty of a 10 days adjunctive therapy with colloidal bismuth subcitrate to a standard triple therapy combining esomeprazole, , amoxicillin and metronidazole for eradicating Helicobacter Pylori in children

A.3.2

Name or abbreviated title of the trial where available

Bismuth based quadruple therapy 10 days in children

A.4.1

Sponsor's protocol code number

CBS-EAM-10d

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	Hôpital Universitaire Des Enfants Reine Fabiola
B.1.3.4	Country	Belgium
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	HUDERF
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hôpital Universitaire Des Enfants Reine Fabiola
B.5.2	Functional name of contact point	Clinical Research Unit
B.5.3	Address:
B.5.3.1	Street Address	Avenue J.J. Crocq 15
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1020
B.5.3.4	Country	Belgium
B.5.4	Telephone number	00322477.36.54
B.5.5	Fax number	00322477.30.99
B.5.6	E-mail	bernard.wenderickx@huderf.be

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	De-Notlab
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma
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	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	TRIPOTASSIUM DICITRATOBISMUTHATE
D.3.9.1	CAS number	57644-54-9
D.3.9.3	Other descriptive name	TRIPOTASSIUM DICITRATOBISMUTHATE
D.3.9.4	EV Substance Code	SUB22602
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	120
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

Helicobacter pylory infection

E.1.1.1

Medical condition in easily understood language

Helicobacter pylory infection

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019377
E.1.2	Term	Helicobacter pylori infection
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

To assess the elimination rate of H. pylori infection in children aged 6 to 17 years using a combination of bismuth sub-citrate, esomeprazole, amoxicillin and metronidazole given for 10 days

E.2.2

Secondary objectives of the trial

1) To assess the safety of a combination of bismuth sub-citrate, esomeprazole, amoxicillin and metronidazole given for 10 days in children aged 6 to 17 years.
2) To assess patient’s adherence to a combination of bismuth sub-citrate, esomeprazole, amoxicillin and metronidazole given for 10 days in children aged 6 to 17 years
3) To assess the effect of antimicrobial resistance on the success rate of a combination of bismuth sub-citrate, esomeprazole, amoxicillin and metronidazole given for 10 days in children aged 6 to 17 years
4) Microbiome analysis

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Paediatric subjects aged 6 to 17 years of either gender
• Body weight ≥ 20kg
• H. pylori gastritis confirmed by positive histology and culture with antimicrobial susceptibility testing.
• Subject able to swallow tablets
• All girls of child-bearing potential must have a negative urine pregnancy test at Visit 1
• If sexually active, girls of child-bearing potential and boys whose partner is of child-bearing potential agree to use highly effective method of birth control during the trial.
• In the Investigator’s opinion, patient is willing and able to comply with all trial requirements specified in this protocol.
• Subjects (or their legally-acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Assent is also required of children capable of understanding the nature of the study (typically older than 11 years of age).

E.4

Principal exclusion criteria

• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
• Have a history of significant renal or hepatic impairment.
• Have an erosive esophagitis or peptic ulcer disease in the gastric or the duodenal mucosa.
• Have received proton pump inhibitors within 2 weeks prior to first administration of study agent.
• Have received any antimicrobial agent within 4 weeks prior to first administration of study agent.
• Require routine use (≥ 2 times per week) of non steroidal anti-inflammatory drug (NSAID)
• Are under any immunosuppressive agent
• Are under oral or IV steroids
• Scheduled elective surgery or any procedures requiring general anaesthesia during the trial.
• Known allergies or a known hypersensitivity to any Study Drugs or their excipients.
• Contraindication for any of the Study Drugs
• Any condition that, in the opinion of the Investigator, would compromise the well-being of the subject or the study or prevent the subject fromm meeting or performing study requirements.
• Participants who are participating or have participated in another study involving an investigational product in the past 12 weeks.

E.5 End points

E.5.1

Primary end point(s)

13C-urea breath test

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 10

E.5.2

Secondary end point(s)

1) Reporting of Adverse Event and Serious Adverse Event
2) Patient compliance based on patient diary card and study drug accountability
3) 13C-urea breath test & Antimicrobial susceptibility testing
4) Stool sampling

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Safety reporting throughout the study (Visit Week 0 to Visit Week 10)
2) Visit Week 2
3) Visit Week 10
4) Visit Week 0 & Visit Week 10

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

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.8.5

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

End of Trial = Last patient, last visit.
Earlier study closure may occur if the "per protocol" eradication rate is significantly below the target of 90% at intermediate analysis (performed every 6 monts or after inclusion of 50 patients whaterver come first)

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

Yes

F.1.1

Number of subjects for this age range:

120

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children < 18 years old

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

120

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)

If a patient has been withdrawal from the study for any reason or if the study treatment fails to eliminate the infection, a rescue treatment will be proposed. If the infecting strain is sensitive to clarithromycin, a triple therapy containing esomeprazole, amoxicillin and clarithromycin for 14 days will be proposed. In all the other cases, a second upper GI endoscopy will be proposed to obtain a secondary antimicrobial susceptibility profile and a tailored treatment will be proposed.

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

2017-06-19

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-09-16

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