Clinical Trials Register

Summary
EudraCT Number:	2008-007292-25
Sponsor's Protocol Code Number:	GIU-5-ASA 1.2MMx-02-08
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:	2009-03-16
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2008-007292-25

A.3

Full title of the trial

AN OPEN, PILOT PHASE III, RANDOMIZED CLINICAL TRIAL TO ASSESS THE TISSUTAL PHARMAKINETICS OF MESALAZINE TABLETS IN PATIENTS WITH MILD TO MODERATE LEFT-SIDED ULCERATIVE COLITIS IN ACTIVE PHASE

A.3.2

Name or abbreviated title of the trial where available

GIU-5-ASA1.2 MMx-02-08

A.4.1

Sponsor's protocol code number

GIU-5-ASA 1.2MMx-02-08

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GIULIANI
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	MEZAVANT
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire Pharmaceutical Contracts Ltd
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	Information not present in EudraCT
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	Mesalazine
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	1.2
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	ASACOL
D.2.1.1.2	Name of the Marketing Authorisation holder	GIULIANI SpA
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	Gastro-resistant tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Mesalazine
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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

Patients with established diagnosis of left-sided UC (rectum-sigmoid colon or colon up to the splenic flexure)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10024123
E.1.2	Term	Left-sided ulcerative (chronic) colitis

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 colonic/rectal intramucosal concentrations of 5-ASA, ensured by a total daily dose of 4.8 g of either oral 5-ASA MMx or Asacol for the time to remission, or, if the remission is not achieved, for a maximum period of 8 weeks, in patients with mild to moderate left-sided ulcerative colitis and in acute phase at the time of the randomization.

E.2.2

Secondary objectives of the trial

To evaluate the colonic/rectal intramucosal concentrations of N-acetyl-5-ASA ensured by a total daily dose of 4.8 g of either oral 5-ASA MMx or Asacol for the time to remission, or, if the remission is not achieved, for a maximum period of 8 weeks, in the study patient population. To compare the time to remission between the two treatment groups. To compare the use of corticosteroids as rescue medication between the two treatment groups. To assess the safety and tolerability of 5-ASA MMx 4.8 g/day in the treatment of Ulcerative Colitis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Written informed consent. 2.Non-pregnant female. If appropriate , urine-test performed prior randomization. 3.Outpatients, male or female, aged 18-75 years. 4.Patients with established diagnosis of left-sided UC (rectum-sigmoid colon or colon up to the splenic flexure). 5.Patients must have either newly diagnosed or relapsing mild to moderate ulcerative colitis (score of 4–10 inclusive on the UC-DAI, with a sigmoidoscopy score of &#8805; 1 and a Physician’s Global Assessment [PGA] of &#8804; 2). 6.Patients who are treated for a minimum of 7 days with a total daily dose of 5-ASA between 1.6 g and 2,4 g at the time of the randomization visit and who are still in acute phase at the time of the randomization visit. 7.Ability to understand and comply with study procedures and restrictions.

E.4

Principal exclusion criteria

1.Patients on maintenance therapy with 5-ASA doses of <1.6 g /day or > 2.4 g /day or who have initiated the treatment with 5-ASA less than 7 days prior randomization. 2.Patients who, in the previous 12 months, had experienced a disease activity unresponsive to a 12-week course with steroids (steroid refractoriness) and those patients in whom steroid dose tapering had been unsuccessful because they returned to be symptomatic (steroid dependence). 3.Patients treated with corticosteroids, oral and/or topical, for at least 28 days prior the screening visit or patients who likely will be treated with oral and/or topical corticosteroids during the study. 4.Patients treated with azathioprine or any immunosuppressant for at least 12 months prior the screening visit. 5.A history of current or recurrent disease, other than UC, that could interfere with the interpretation of the study results or affect absorption or disposition of the study drug. This includes: peptic ulceration and gastrointestinal bleeding, celiac disease, lactose intolerance, pancreatitis, Crohn’s disease or proctitis only (where the extent of inflammation &#8804; 10 cm from the anus). 6.A history of colon surgery performed within the past 12 months prior to the first dose of study drug, with the exception of an appendectomy. 7.Patients with asthma, if ASA sensitive. 5-ASA compounds are contraindicated with history of sensitivity or allergic reaction to salicylates/aspirin or a suspected history of intolerance or hypersensitivity to the study drug (mesalazine or salicylates), and related drug, or any of the stated ingredients. 8.History of concurrent malignancy or evidence of dysplasia in the colon specimen. 9.Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, including infections, or any medical disorder that may require treatment (e.g. renal or hepatic impairment) or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures. 10.Evidence or suspect of positive test for HIV, HBsAg, or HCV 11.Patients presenting poor reliability (e.g. alcohol or drug abuse, bad mental conditions). 12.Patients who used another investigational agent or who took part in a clinical trial within the last 90 days prior to baseline.

E.5 End points

E.5.1

Primary end point(s)

The primary end-point is to evaluate the colonic/rectal intramucosal concentrations of 5-ASA ensured by a total daily dose of 4.8 g of either oral 5-ASA MMx or Asacol at the Time of Remission or at 8 weeks, if the Remission is not achieved, in patients with mild to moderate left-sided ulcerative colitis and in acute phase at the time of the randomization

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

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)

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

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

Yes

E.8.1.7.1

Other trial design description

prospettico

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

Yes

E.8.2.3.1

Comparator description

- same IMP used at different dosage

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

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

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	40

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

2009-03-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-01-26

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

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