Clinical Trials Register

Summary
EudraCT Number:	2015-002969-27
Sponsor's Protocol Code Number:	PMF104PD1-2-3/2013
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-10-17
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

France - ANSM

A.2

EudraCT number

2015-002969-27

A.3

Full title of the trial

A RANDOMISED, SINGLE-BLIND, ACTIVE CONTROLLED, MULTI-CENTRE TRIAL TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, ACCEPTABILITY AND PALATABILITY OF PMF104 COMPARED TO A CONVENTIONAL PEG-ELECTROLYTE SOLUTION IN CHILDREN AGED FROM 2 TO LESS THAN 6, FROM 6 TO LESS THAN 12 AND ADOLESCENTS FROM 12 TO LESS THAN 18 YEARS OF AGE REQUIRING A DIAGNOSTIC PROCEDURE CONCERNING THE COLON
(EMA Decision P/019/2017 on the acceptance of modification of Paediatric Investigation Plan)

Essai multicentrique, randomisé, en simple aveugle, contrôlé par substance active, visant à évaluer l’efficacité, la sécurité d’emploi, la tolérance, l’acceptabilité et la palatabilité du PMF104 par comparaison à une solution électrolytique conventionnelle contenant du PEG, chez des enfants âgés de 2 ans à moins de 6 ans, de 6 ans à moins de 12 ans et chez des adolescents âgés de 12 ans à moins de 18 ans, devant subir une procédure à visée diagnostique concernant le côlon
(Décision de l’EMA P/019/2017 relative à l’approbation de modification du Plan d’Investigation Pédiatrique)

A.3.1

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

Clinical trial aimed at evaluating the efficacy, safety, tolerability, acceptability and palatability of PMF104 in children from 2 to less than 18 years old

Essai clinique visant à évaluer l’efficacité, la sécurité d’emploi, la tolérance, l’acceptabilité et la palatabilité du PMF104 chez des enfants âgés de 2 ans à moins de 18 ans

A.4.1

Sponsor's protocol code number

PMF104PD1-2-3/2013

A.5.4

Other Identifiers

Name:

CRO-15-125

Number:

CRO code

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/051/2014

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Alfa Wassermann S.p.A.
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	Alfa Wassermann S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sigma-tau i.f.r S.p.A
B.5.2	Functional name of contact point	Regulatory Development and QA, R&D
B.5.3	Address:
B.5.3.1	Street Address	Via Pontina Km 30,400
B.5.3.2	Town/ city	Pomezia
B.5.3.3	Post code	00071
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390691393657
B.5.5	Fax number	00390631035080
B.5.6	E-mail	giulia.bruno@sigma-tau.it

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	Clensia®
D.2.1.1.2	Name of the Marketing Authorisation holder	Alfa Wassermann S.p.A. (Italy)
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Powder for oral solution in sachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasogastric use (Noncurrent) Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Macrogol 4000
D.3.9.1	CAS number	25322-68-3
D.3.9.3	Other descriptive name	MACROGOL 4000 PH. EUR.
D.3.9.4	EV Substance Code	SUB172298
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	52.500
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium sulfate, anhydrous
D.3.9.1	CAS number	7757-82-6
D.3.9.3	Other descriptive name	SODIUM SULPHATE
D.3.9.4	EV Substance Code	SUB20969
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3.750
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Simeticone
D.3.9.1	CAS number	8050-81-5
D.3.9.3	Other descriptive name	SIMETICONE
D.3.9.4	EV Substance Code	SUB04403MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.080
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium citrate
D.3.9.1	CAS number	68-04-2
D.3.9.3	Other descriptive name	SODIUM CITRATE
D.3.9.4	EV Substance Code	SUB34328
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.863
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Citric acid anhydrous
D.3.9.1	CAS number	77-92-9
D.3.9.3	Other descriptive name	CITRIC ACID ANHYDROUS
D.3.9.4	EV Substance Code	SUB29050
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.813
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sodium chloride
D.3.9.1	CAS number	7647-14-5
D.3.9.3	Other descriptive name	SODIUM CHLORIDE
D.3.9.4	EV Substance Code	SUB12581MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.730
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Potassium chloride
D.3.9.1	CAS number	7447-40-7
D.3.9.3	Other descriptive name	POTASSIUM CHLORIDE
D.3.9.4	EV Substance Code	SUB12559MIG
D.3.10	Strength
D.3.10.1	Concentration unit	g gram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.370
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	KLEAN-PREP
D.2.1.1.2	Name of the Marketing Authorisation holder	Norgine Italia S.r.l
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Powder for oral solution in sachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasogastric use (Noncurrent) Oral use
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

Need of bowel cleansing in order to perform a colonoscopy or any other diagnostic or therapeutic procedure concerning the colon.

Besoin de vider l'intestin avant une coloscopie ou d'autres procédures diagnostiques ou thérapeutiques sur le côlon.

E.1.1.1

Medical condition in easily understood language

Bowel cleansing before diagnostic or therapeutic procedures concerning colon.

Le nettoyage du côlon avant toute procédure diagnostique ou thérapeutique sur le côlon.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10066943
E.1.2	Term	Bowel preparation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 evaluate the efficacy of PMF104 compared to KLEAN-PREP in children aged from 2 to less than 18 years old requiring a diagnostic procedure of the colon

Évaluer l’efficacité du PMF104 par comparaison à KLEAN-PREP chez des enfants âgés de 2 ans à moins de 18 ans devant subir une procédure à visée diagnostique concernant le côlon

E.2.2

Secondary objectives of the trial

To evaluate the efficacy, safety, tolerability, acceptability and palatability of PMF104 compared to KLEAN-PREP in children aged from 2 to less than 18 years old requiring a diagnostic procedure of the colon

Évaluer l’efficacité, la sécurité d’emploi, la tolérance, l’acceptabilité et la palatabilité du PMF104 par comparaison à KLEAN-PREP chez des enfants âgés de 2 ans à moins de 18 ans devant subir une procédure à visée diagnostique concernant le côlon

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients aged from 2 to less than 18 years undergoing elective colonoscopy
2. Female subjects currently either of:
non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is surgically sterilised via documented hysterectomy or bilateral tubal ligation),
or
child bearing potential: the subject is eligible to enter and participate in this study if she is not lactating and has a negative pregnancy test (only menstruated females) and agrees to abstain from intercourses until the colonoscopy is performed
3. Patients whose parents/legal representatives have been thoroughly informed of the aim of the study procedures and provided signed and dated written informed consent
4. Children aged from 6 to less than 12 years providing informed assent whenever possible
5. Adolescents aged from 12 to less than 18 years providing informed assent
6. Ability of the subjects and/or their parents/legal representatives to understand and comply with protocol requirements, instructions and protocol-stated restrictions

1. Patients de sexe masculin et féminin âgés de 2 ans à moins de 18 ans pendant toute la durée de l’étude subissant une coloscopie élective
2. Patients de sexe féminin qui actuellement :
Ne sont pas en âge de procréer (c.-à-d. incapable sur le plan physiologique de débuter une grossesse, incluant toute femme chirurgicalement stérilisée par hystérectomie ou ligature bilatérale des trompes documentée),
ou
Sont en âge de procréer : la patiente est éligible pour entrer et participer à cette étude si elle n’allaite pas et a un test de grossesse négatif (uniquement pour les femmes ayant des menstruations), et si elle consent à s’abstenir de rapports sexuels jusqu’à la réalisation de la coloscopie
3. Patients dont les parents/représentants légaux ont été soigneusement informés de l’objectif des procédures de l’étude et ont fourni un consentement éclairé par écrit et signé
4. Enfants âgés de 6 ans à moins de 12 ans fournissant un assentiment éclairé, dans la mesure du possible
5. Adolescents âgés de 12 ans à moins de 18 ans fournissant un assentiment éclairé
6. Patients et/ou leurs parents/représentants légaux aptes à comprendre et à se conformer aux exigences du protocole, aux instructions et aux restrictions définies dans le protocole.

E.4

Principal exclusion criteria

1. Requirement for urgent colonoscopy
2. Gastrointestinal obstruction or perforation
3. Bowel pseudo-obstruction
4. Gastric retention
5. Toxic colitis
6. Toxic megacolon
7. Known or suspected hypersensitivity to the active or other ingredients of both test product and reference product
8. Clinically significant electrolyte imbalance
9. Prior intestinal resection
10. Structural abnormality of the lower gastrointestinal (GI) tract
11. Known metabolic (particularly phenylketonuria), hepatic, renal or cardiac disease
12. Congestive heart failure (NYHA class III and IV)
13. Known pregnancy
14. Subject who have participated in another clinical trial or have taken an investigational drug within the last 3 months prior screening

1. Besoin d’une coloscopie en urgence
2. Occlusion ou perforation gastro-intestinale
3. Pseudo-occlusion intestinale
4. Rétention gastrique
5. Colite toxique
6. Mégacôlon toxique
7. Hypersensibilité connue ou suspectée à la substance active ou à d’autres composants du produit test et du produit de référence
8. Déséquilibre électrolytique cliniquement significatif
9. Résection intestinale antérieure
10. Anomalie structurelle du tractus gastro-intestinal (GI) inférieur
11. Maladie métabolique (en particulier, phénylcétonurie), hépatique, rénale, ou cardiaque connue
12. Insuffisance cardiaque congestive (classe NYHA III ou IV)
13. Grossesse connue
14. Sujet ayant participé à un autre essai clinique ou ayant pris un médicament expérimental dans les 3 mois précédent la sélection.

E.5 End points

E.5.1

Primary end point(s)

To compare the efficacy in terms of colon cleansing according the Boston Bowel Preparation Scale (BBPS) score on the day of the diagnostic procedure, to be determinated blindly by the endoscopist upon completion of the examination

Efficacité comparative en termes de nettoyage du côlon, selon le score de l'échelle de préparation colique de Boston (Boston Bowel Preparation Scale, BBPS) le jour de la procédure diagnostique, à déterminer en aveugle par le coloscopiste après la fin de l'examen

E.5.1.1

Timepoint(s) of evaluation of this end point

Upon completion of the examination (Visit 3, Day 2)

à la fin de la coloscopie (Visite 3, Jour 2)

E.5.2

Secondary end point(s)

1. Efficacy:
- Time to reach clear watery stools
- Proportion of patients in whom caecal intubation was achieved during colonoscopy
- Proportion of patients achieving a BBPS score grater than or equal to 5
2. Proportion of patients that needed a rescue dose
3. Safety assessment
4. Tolerability assessment
5. Compliance assessment
6. Acceptability assessment
7. Palatability assessment

1. Efficacité :
- Délai pour obtenir des selles aqueuses claires
- Proportion de patients chez qui une intubation cæcale a été réalisée au cours de la coloscopie
- Proportion de patients atteignant un score BBPS ≥ 5
2. Proportion de patients qui ont besoin d’une dose de secours
3. Évaluations de la sécurité d’emploi et de la tolérance
4. Évaluations de la tolérance
5. Évaluations de la observance
6. Évaluations de l’acceptabilité
7. Évaluations de la palatabilité

E.5.2.1

Timepoint(s) of evaluation of this end point

During /after the treatment

Pendant / après le traitement

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability, acceptability and palatability

Tolérance, acceptabilité et palatabilité

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

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

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

LVLS

Dernière visite du dernier patient

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

Number of subjects for this age range:

430

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:

262

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

168

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2018-10-17.

Yes

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

Minors

Mineurs

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

430

F.4.2.2

In the whole clinical trial

430

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

Aucun

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

2017-08-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-03-05

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