Clinical Trials Register

Summary
EudraCT Number:	2016-000516-15
Sponsor's Protocol Code Number:	5-ASA/12/2015
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-16
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

2016-000516-15

A.3

Full title of the trial

Intestinal mucosal concentrations from three mesalazine pharmaceutical formulations and correlation with efficacy in patients with mild/moderate ulcerative colitis

Valutazione delle concentrazioni di tre formulazioni di mesalazina nella mucosa intestinale e correlazione con l’efficacia in pazienti con retto-colite ulcerosa lieve/moderata.

A.3.1

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

Intestinal concentrations and efficacy of different mesalazine tablets in patients with ulcerative colitis.

Valutazioni delle concentrazioni intestinali e dell'efficacia di diverse compresse di mesalazina in paziente con colite ulcerosa.

A.3.2

Name or abbreviated title of the trial where available

Tissue concentrations and efficacy of three mesalazine formulations.

Concentrazioni tissutali ed efficacia di tre formulazioni di mesalazina.

A.4.1

Sponsor's protocol code number

5-ASA/12/2015

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	CONSORZIO UNIVERSITARIO UNIFARM
B.1.3.4	Country	Italy
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	Consorzio Universitario Unifarm
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	CONSORZIO UNIVERSITARIO UNIFARM
B.5.2	Functional name of contact point	DIREZIONE UNIFARM
B.5.3	Address:
B.5.3.1	Street Address	VIA A. DORIA, 21
B.5.3.2	Town/ city	CATANIA
B.5.3.3	Post code	95125
B.5.3.4	Country	Italy
B.5.4	Telephone number	0957167514
B.5.5	Fax number	0952865220
B.5.6	E-mail	direzione@unifarm.org

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	PENTASA - 500MG COMPRESSE A RILASCIO MODIFICATO 50 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	FERRING S.P.A.
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.3.1	Product name	PENTASA
D.3.2	Product code	[/]
D.3.4	Pharmaceutical form	Modified-release 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	acido 5-aminosalicilico
D.3.9.2	Current sponsor code	/
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	500
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Yes
D.2.1.1.1	Trade name	PENTACOL
D.2.1.1.2	Name of the Marketing Authorisation holder	SOFAR S.P.A.
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.3.1	Product name	PENTACOL
D.3.2	Product code	[/]
D.3.4	Pharmaceutical form	Modified-release 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	acido 5-aminosalicilico
D.3.9.2	Current sponsor code	/
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	800
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 3
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	MESALAZINA Sandoz 500 mg compresse rivestite
D.2.1.1.2	Name of the Marketing Authorisation holder	SANDOZ S.P.A.
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.3.1	Product name	MESALAZINA SANDOZ
D.3.2	Product code	/
D.3.4	Pharmaceutical form	Modified-release 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	acido 5-aminosalicilico
D.3.9.2	Current sponsor code	/
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	500
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Ulcerative colites

Rettocolite ulcerosa

E.1.1.1

Medical condition in easily understood language

Inflammatory colonic disease

Malattia infiammatoria del colon

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	10009900
E.1.2	Term	Colitis ulcerative
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluation of tissue concentrations in endoscopic intestinal biopsies of different mesalazine formulations

Valutazione delle concentrazioni tissutali in biopsie intestinali di tre diverse formulazioni di mesalazina

E.2.2

Secondary objectives of the trial

Efficacy of the three formulations and correlation with tissue concentration in endoscopic intestinal biopsies.
Safety profile of the three formulations.

Efficacia delle tre formulazioni e correlazione con le concentrazioni tissutali rilevate alle biopsie intestinali.
Profilo di sicurezza delle tre formulazioni.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Adults male and female aged 18 to 65 years.
• Patients with mildly/moderately active ulcerative colitis (Mayo scoregreater than or equal to 3 but less than or equal to 10 and with an endoscopy score of at least 1).
• Willing and ability to give informed consent.

Pazienti di età >=18 anni e< =65 anni.
Pazienti affetti da rettocolite ulcerosa lieve/moderata (Mayo score >=3 ma <=10 e con uno score endoscopico di almeno 1).
Capacità e volontà di sottoscrivere il consenso informato.

E.4

Principal exclusion criteria

• Patients with severe ulcerative colitis (Mayo score greater than 10).
• Ulcerative colitis only affecting rectum (proctitis).
• Treatment with topical aminosalicylate.
• Treatment with 5-aminosalicylic acid (5-ASA) at a dose of >2.0g/day within 1 week prior to randomisation.
• Failed treatment with a mesalazine dose of > 2.0 g/day within 4 weeks prior randomization.
• Treatment with systemic or rectal steroids within 4 weeks prior to randomization.
• Treatment with immunosuppressants within 6 weeks prior to randomization.
• Treatment with infliximab or other biologics within 3 months prior to randomization.
• Treatment with anti-diarrheals within 7 days prior to randomization.
• History of colectomy or partial colectomy.
• Gastrointestinal infection.
• Immediate or significant risk of toxic megacolon.
• Hypersensitivity to salicylates, aspirin, sulfasalazine or 5-ASA.
• Renal and/or hepatic failure.
• Women who are pregnant, nursing or planning pregnancy during the course of the study.
• Female partecipants of child-bearing potential, unless willing to use contraception during the study.
• Enrollment in another study protocol within 30 days prior to randomization.
• History of alcohol or drug abuse.
• Any other significant disorders which, in the opinion of the investigator, may influence the participation in the study or affect study result.

Pazienti con rettocolite ulcerosa severa (Mayo score >10).
Rettocolite ulcerosa limitata al retto (proctite).
Trattamento con amino-salicilati topici.
Trattamento con acido 5-amino-salicilico (5-ASA) a dosi >2 g/die nella settimana precedente la randomizzazione.
Fallimento di un trattamento con mesalazina a dosi >2 g/die entro 4 settimane prima della randomizzazione.
Trattamento con steroidi sistemici o rettali nelle 4 settimane precedenti la randomizzazione.
Trattamento con immunosoppressori nelle 6 settimane precedenti la randomizzazione.
Trattamento con infliximab o altri biologici nei 3 mesi precedenti la randomizzazione.
Trattamento con anti-diarroici nei 7 giorni precedenti la randomizzazione.
Storia di colectomia totale o parziale.
Infezione gastrointestinale.
Rischio immediato o significativo di megacolon tossico
Ipersensibilità nota ai salicilati, all’aspirina, alla sulfasalzina o al 5-ASA.
Insufficienza renale e/o epatica.
Donne in gravidanza, o che programmano una gravidanza durante il periodo di studio, e donne in allattamento.
Donne potenzialmente in età fertile non disposte a ricorrere a misure contraccettive efficaci.
Partecipazione in un altro studio nei 30 giorni precedenti la randomizzazione.
Storia di abuso di droga, farmaci o alcol.
Qualsiasi altro disturbo che, secondo l’opinione dello sperimentatore, potrebbe influenzare la partecipazione allo studio o i risultati

E.5 End points

E.5.1

Primary end point(s)

Tissue concentrations in endoscopic intestinal biopsies of different mesalazine
formulations

Concentrazioni tissutali in biopsie intestinali di tre diverse formulazioni di mesalazina

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluated after 8 weeks of treatment with Mesalazine

Valutazione dopo 8 settimane dal trattamento con Mesalazina

E.5.2

Secondary end point(s)

Clinical response defined as a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1.; Clinical remission defined as a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point; Mucosal healing defined as an absolute subscore for endoscopy of 0 or 1; Time to remission.; Remission rate.; Maintainance of remission

Risposta clinica definita come riduzione del Mayo score basale di almeno 3 punti ed almeno il 30%, con riduzione del sub-score per sanguinamento rettale di almeno 1 punto o di un sub-score assoluto di sanguinamento rettale di 0 o 1.; Remissione clinica definita come Mayo score totale =2 punti, con nessun sub-score superiore ad 1.; Guarigione delle lesioni della mucosa definita come sub-score endoscopico di 0 o 1.; Tempo alla remissione; Tasso di remissione.; Mantenimento della remissione.

E.5.2.1

Timepoint(s) of evaluation of this end point

Clinical respone will be assed at weeks 8; Clinical remission will be assessed at weeks 8; Mucosal healing will be assessed at weeks 8; Clinical Mayo score will be evaluated every 2 weeks from treatment start till weeks 8, and at weeks 12.; The evaluation of remmission rate will be performed at weeks 8; Up to the follow-up date

La valutazione della risposta clinica sarà effettuata alla settimana 8.; La valutazione della remissione clinica sarà effettuata alla settimana 8; La valutazione della guarigione della mucosa sarà effettuata alla settimana 8; Il Mayo score clinico sarà valutato ogni 2 settimane dall'inizio del trattamento fino alla settimana 8, ed alla settimana 12.; La valutazione del tasso di remissione sarà effettuata alla settimana 8.; Fino al follow-up

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

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

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

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.8.6 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

Information not present in EudraCT

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

LVSL

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)

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

At the end of the study patients could be followed at the same clinical center, in accordance with the timing and procedures required by current clinical practice.

Al termine dello studio i pazienti potranno essere seguiti presso lo stesso centro clinico, secondo i tempi e le modalità previste dalla pratica clinica corrente.

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

2016-05-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-14

P. End of Trial
P.	End of Trial Status	Completed

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