Clinical Trials Register

Summary
EudraCT Number:	2013-000452-18
Sponsor's Protocol Code Number:	CB-17-03/01
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:	2013-02-18
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

2013-000452-18

A.3

Full title of the trial

Staining efficacy and safety of Methylene Blue enemas in patients undergoing flexible rectosigmoidoscopy

Efficacia della colorazione e sicurezza di clisteri di blu di metilene in pazienti sottoposti a rettosigmoidoscopia flessibile

A.3.1

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

Staining efficacy and safety of Methylene Blue enemas in patients undergoing rectum and sigma examination for various reasons

Efficacia della colorazione e sicurezza di clisteri di blu di metilene in pazienti che devono sottoporsi ad esame endoscopico del retto e del sigma per vari motivi

A.3.2

Name or abbreviated title of the trial where available

Methylene Blue enema staining in patients

Colorazione con clistere di blu di metilene in pazienti

A.4.1

Sponsor's protocol code number

CB-17-03/01

A.5.4

Other Identifiers

Name:

Study protocol

Number:

CRO-13-111

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	Cosmo Technologies Ltd.
B.1.3.4	Country	Ireland
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	Cosmo Technologies Ltd.
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CROSS S.A.
B.5.2	Functional name of contact point	Study Management
B.5.3	Address:
B.5.3.1	Street Address	Via F.A. Giorgioli
B.5.3.2	Town/ city	Arzo
B.5.3.3	Post code	6864
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41916300510
B.5.5	Fax number	+41916300511
B.5.6	E-mail	corporate@croalliance.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	No
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	Methylene Blue enema 0.002%
D.3.2	Product code	CB-17-03
D.3.4	Pharmaceutical form	Enema
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Rectal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	methylthioninium chloride
D.3.9.2	Current sponsor code	CB-17-01
D.3.9.3	Other descriptive name	METHYLENE BLUE
D.3.9.4	EV Substance Code	SUB21957
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.002
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	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	No
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	Methylene Blue enema 0.02%
D.3.2	Product code	CB-17-03
D.3.4	Pharmaceutical form	Enema
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Rectal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	methylthioninium chloride
D.3.9.2	Current sponsor code	CB-17-03
D.3.9.3	Other descriptive name	METHYLENE BLUE
D.3.9.4	EV Substance Code	SUB21957
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.02
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

Out-patients of both sexes with indication for diagnostic flexible rectosigmoidoscopy.

Pazienti ambulatoriali di entrambi i sessi con l’indicazione ad effettuare una rettosigmoidoscopia flessibile.

E.1.1.1

Medical condition in easily understood language

Out-patients of both sexes with indication for performing an examination of rectum and sigma for various reasons

Pazienti ambulatoriali di entrambi i sessi con l’indicazione ad effettuare un esame del retto e del sigma per vari motivi

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10016774
E.1.2	Term	Flexible sigmoidoscopy
E.1.2	System Organ Class	100000004848

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 the evaluation of the mucosal staining efficacy after single rectal dose of two Methylene Blue enema formulations containing, respectively, 0.002% methylene blue (Formulation A) and 0.02% methylene blue (Formulation B), in patients undergoing a rectosigmoidoscopy for various reasons.

Con questo studio clinico si vuole valutare l’efficacia nella colorazione della mucosa intestinale dopo somministrazione di una dose singola rettale di due formulazioni di clistere di blu di metilene contenenti rispettivamente blu di metilene allo 0.002% (Formulazione A) e blu di metilene allo 0.02% (Formulazione B) a pazienti sottoposti a rettosigmoidoscopia per vari motivi.

E.2.2

Secondary objectives of the trial

Bowel cleansing quality evaluated according to a four-point scoring system after administration of Methylene Blue enema and of the cleansing enema.
To collect data about safety and tolerability of the two test Methylene Blue enema formulations.
Evaluation of the number of mucosal lesions detected with the two test Methylene Blue enema formulations and of the proportion of subjects with at least one mucosal lesion.

Valutazione della qualità della pulizia del retto e del sigmoide con assegnazione di un punteggio dopo somministrazione delle due formulazioni di clistere di blu di metilene.
Valutazione del profilo di sicurezza e tollerabilità di due formulazioni di clistere di blu di metilene.
Valutazione del numero di lesioni della mucosa identificate con le due formulazioni di clistere di blu di metilene e della proporzione di soggetti con almeno una lesione della mucosa.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Age: ≥18 year old;
2.Rectosigmoidoscopy: out-patients with indication for rectosigmoidoscopy;
3.Contraception (both males and females): either sterile subjects or subjects practising at least one reliable method of contraception or females in post-menopausal status for at least 1 year;
4.Informed Consent: signed written informed consent prior to inclusion in the study.

1. età maggiore o uguale a 18 anni;
2. pazienti ambulatoriali con l’indicazione ad effettuare una rettosigmoidoscopia;
3. dovranno essere sterili o utilizzare almeno un metodo contraccettivo affidabile o essere in post-menopausa da almeno un anno;
4. dovranno aver firmato il consenso informato prima dell’inclusione nello studio.

E.4

Principal exclusion criteria

1.Pregnancy: pregnant or lactating women or at a risk of becoming pregnant;
2.Allergy: known or suspected hypersensitivity to the active principle; history of anaphylaxis to drugs or allergic reactions in general;
3.Diseases: known or suspected gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, heart failure (Class III or IV), serious cardiovascular disease, severe liver failure, methaemoglobinemia, any other relevant disease that might interfere with the aim of the study;
4.Comprehension: inability to comprehend the full nature and purpose of the study and unwillingness to co-operate with the investigator and to comply with the requirements of the entire study.

1.donne incinte o in allattamento o a rischio di gravidanza;
2.ipersensibilità accertata/presunta al principio attivo; storia di allergia ai farmaci o di reazioni allergiche in generale;
3.accertate/presunte ostruzioni o perforazioni gastrointestinali, megacolon tossico, resezione maggiore del colon, insufficienza cardiaca (Classe III o IV), gravi malattie cardiovascolari, insufficienza epatica grave, metaemoglobinemia o qualsiasi altra patologia rilevante che possa interferire con gli scopi del presente studio;
4.incapacità di comprendere completamente la natura e lo scopo dello studio e di cooperare con lo Sperimentatore ottemperando a tutte le procedure richieste dallo studio.

E.5 End points

E.5.1

Primary end point(s)

Mucosal staining efficacy of the two test Methylene Blue enema.

Efficacia nella colorazione della mucosa delle due formulazioni di clistere di blu di metilene.

E.5.1.1

Timepoint(s) of evaluation of this end point

Mucosal staining efficacy will be scored during the rectosigmoidoscopy performed on day 1 (Visit 2), according to a subjective four-point scale scoring system.

L'efficacia nella colorazione della mucosa sarà valutata durante la rettosigmoidoscopia che sarà eseguita il giorno 1 (Visita 2), assegnando un punteggio secondo una scala a quattro punti.

E.5.2

Secondary end point(s)

Bowel cleansing quality evaluated according to a four-point scoring system after administration of Methylene Blue enema and of the cleansing enema.
Safety and tolerability (treatment emergent adverse events, vital signs (blood pressure, heart rate, peripheral oxygen saturation)) of the two test Methylene Blue enema formulations.
Evaluation of the number of mucosal lesions detected and of the proportion of subjects with at least one mucosal lesion.

Valutazione della qualità della pulizia del retto e del sigmoide con assegnazione di un punteggio dopo somministrazione delle due formulazioni di clistere di blu di metilene.
Valutazione del profilo di sicurezza e tollerabilità (eventi avversi, segni vitali (pressione sanguigna, frequenza cardiaca, saturazione d'ossigeno)) delle due formulazioni di clistere di blu di metilene.
Valutazione del numero di lesioni della mucosa e della proporzione di soggetti con almeno una lesione della mucosa.

E.5.2.1

Timepoint(s) of evaluation of this end point

Bowel cleansing quality will be scored during the rectosigmoidoscopy performed on day 1 (Visit 2) according to a four-point scoring system. Safety and tolerability will be evaluated prior, during and after the rectosigmoidoscopy.
During the rectosigmoidoscopy the Investigator will report the number of detected mucosal lesions.

La valutazione della qualità della pulizia del retto e del sigmoide verrà effettuata durante la rettosigmoidoscopia effettuata il giorno 1 (Visita 2), assegnando un punteggio, secondo una scala di punteggio a 4 punti.
Sicurezza e tollerabilità saranno valutate prima, durante e dopo la rettosigmoidoscopia.
Il numero delle lesioni della mucosa sarà individuato dallo Sperimentatore durante la rettosigmoidoscopia.

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.7.1

Other trial design description

a due bracci e due gruppi consecutivi

Two arms, two consecutive groups

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

LVLS

Ultima visita dell'ultimo soggetto

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

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:

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

F.4 Planned number of subjects to be included

F.4.1

In the member state

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

2013-03-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-02-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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