Clinical Trials Register

Summary
EudraCT Number:	2013-000923-15
Sponsor's Protocol Code Number:	THILO08
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-05-22
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

Greece - EOF

A.2

EudraCT number

2013-000923-15

A.3

Full title of the trial

A multicenter, double-blind, randomized, parallel arm comparative study for the assessment of the safety and efficacy of azidamfenicol eye drops (Thilocof®/FARMEX) versus tobramycine eye drops (Τobrex®/Alcon) in the treatment of patients with infections of the outer layers of the eye.

Μία πολυκεντρική, διπλά τυφλή, τυχαιοποιημένη συγκριτική κλινική μελέτη παραλλήλων ομάδων ασθενών για την αξιολόγηση της αποτελεσματικότητας και της ασφάλειας της αγωγής με οφθαλμικές σταγόνες αζιθαμφαινικόλης (Thilocof®/ΦΑΡΜΕΞ) έναντι της αγωγής με οφθαλμικές σταγόνες τομπραμυκίνης (Τobrex®/Alcon) στη θεραπεία ασθενών με λοιμώξεις των εξωτερικών χιτώνων του οφθαλμού

A.3.1

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

Azidamfenicol & tobramycin eye drops treatment prospective efficay and safety comparison in infections of the outer layers of the eye

Σύγκριση των θεραπειών με κολλύρια αζιθαμφαινικόλης & τομπραμυκίνης σε λοιμώξεις των εξωτερικών χιτώνων του οφθαλμού

A.4.1

Sponsor's protocol code number

THILO08

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	FARMEX SA
B.1.3.4	Country	Greece
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	FARMEX SA
B.4.2	Country	Greece
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FARMEX SA
B.5.2	Functional name of contact point	Nikolaos Papazoglou
B.5.3	Address:
B.5.3.1	Street Address	132 Kifissou Av., Peristeri
B.5.3.2	Town/ city	Athens
B.5.3.3	Post code	121 31
B.5.3.4	Country	Greece
B.5.4	Telephone number	+30 210 5199230
B.5.5	Fax number	+30 2105144 279

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	THILOCOF 1% Eye Drops Solution
D.2.1.1.2	Name of the Marketing Authorisation holder	FARMEX SA
D.2.1.2	Country which granted the Marketing Authorisation	Greece
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	Azidamfenicol
D.3.2	Product code	1773301
D.3.4	Pharmaceutical form	Eye drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	AZIDAMFENICOL
D.3.9.1	CAS number	13838-08-9
D.3.9.3	Other descriptive name	2-azido-N-((1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl)acetamide
D.3.9.4	EV Substance Code	SUB05654MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	TOBREX 0.3% Eye Drops
D.2.1.1.2	Name of the Marketing Authorisation holder	SA ALCON-COUVREUR NV
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	Tobramycin
D.3.4	Pharmaceutical form	Eye drops, solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TOBRAMYCIN
D.3.9.1	CAS number	32986-56-4
D.3.9.3	Other descriptive name	O-[3-Amino-3-deoxy-α-D-glucopyranosyl-(1→6)]-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribohexopyranosyl-(1→4)]-2-deoxy-D-streptamine
D.3.9.4	EV Substance Code	SUB11134MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
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

Infections of the outer eye layers (mainly bacterial conjuctivitis )

Λοιμώξεις των εξωτερικών χιτώνων του οφθαλμού - (κυρίως μικροβιακή επιπεφυκίτιδα)

E.1.1.1

Medical condition in easily understood language

Bacterial conjuctivitis

Mικροβιακή επιπεφυκίτιδα

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10010742
E.1.2	Term	Conjunctivitis infective
E.1.2	System Organ Class	10021881 - Infections and infestations

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 comparative assessment of the efficacy of azidamfenicol eye drops (Thilocof®/FARMEX) vs. tobramycin eye drops (Τobrex®/Alcon) in the treatement of patients with infections of the outer eye layers (bacterial conjuctivitis )

H αξιολόγηση της αποτελεσματικότητας της αγωγής με οφθαλμικές σταγόνες αζιθαμφαινικόλης (Thilocof®/ΦΑΡΜΕΞ) έναντι της αγωγής με οφθαλμικές σταγόνες τομπραμυκίνης (Τobrex®/Alcon) στη θεραπεία ασθενών με λοιμώξεις των εξωτερικών χιτώνων του οφθαλμού (μικροβιακή επιπεφυκίτιδα

E.2.2

Secondary objectives of the trial

• to evaluate the safety of azidamfenicol eye drops (Thilocof®/FARMEX) vs. tobramycin eye drops (Τobrex®/Alcon) in the treatement of patients with infections of the outer eye layers (bacterial conjuctivitis )
• to explore for any differences in the time of occurence of signs and symptoms improvement between the azidamfenicol eye drops (Thilocof®/FARMEX) vs. tobramycin eye drops (Τobrex®/Alcon) in the treatement of patients with infections of the outer eye layers (bacterial conjuctivitis )
• to explore for any differences in the quality of life between the azidamfenicol eye drops (Thilocof®/FARMEX) vs. tobramycin eye drops (Τobrex®/Alcon) in the treatement of patients with infections of the outer eye layers (bacterial conjuctivitis )

• να ελέγξει την ασφάλεια της τοπικής αγωγής με οφθαλμικές σταγόνες αζιθαμφαινικόλης (Thilocof®/ΦΑΡΜΕΞ) έναντι της αγωγής με οφθαλμικές σταγόνες τομπραμυκίνης (Τobrex®/Alcon) στη θεραπεία ασθενών με λοιμώξεις των εξωτερικών χιτώνων του οφθαλμού.
• να διερευνήσει για τυχόν διαφορές στον χρόνο εμφάνισης της βελτίωσης των συμπτωμάτων και σημείων της νόσου μεταξύ της τοπικής αγωγής με με οφθαλμικές σταγόνες αζιθαμφαινικόλης (Thilocof®/ΦΑΡΜΕΞ) έναντι της αγωγής με οφθαλμικές σταγόνες τομπραμυκίνης (Τobrex®/Alcon)
• να διερευνήσει για τυχόν διαφορές στην ποιότητα ζωής μεταξύ της τοπικής αγωγής με με οφθαλμικές σταγόνες αζιθαμφαινικόλης (Thilocof®/ΦΑΡΜΕΞ) έναντι της αγωγής με οφθαλμικές σταγόνες τομπραμυκίνης (Τobrex®/Alcon).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men and women, of = or > 18 years of age
2. Subjects with a clinical diagnosis of outer eye layer(s) infection (i.e. subjects with a diagnosis of bacterial conjuctivitis, cornea-conjuctivitis, blepharitis or blepharo-conjuctivitis)
3. Subjects who present conjuctival hyperemia and at least one of the following signs:
• purulent of mucopurulent exudate,
• formation of scabs on eyelashes
• redness & thickness of the free eyelash rim
• eyelashes loss (of various degree)
4. Subjects willing to and capable of attending the study visits within the visits' allowed time windows.
5. Subjects who have signed the Informed Consent.

1. Ασθενείς, άνδρες και γυναίκες, ηλικίας = ή > 18 ετών
2. Ασθενείς με κλινική διάγνωση λοιμώξης των εξωτερικών χιτώνων του οφθαλμού (δηλ. ασθενείς με διάγνωση βακτηριακής επιπεφυκίτιδας, κερατοεπιπεφιλύτιδας, βλεφαρίτιδας ή βλεφαρο-επιπεφυκίτιδας))
3. Ασθενείς που κατά την ιατρική εξέταση παρουσιάζουν υπερεμία του επιπεφυκότα και τουλάχιστον ένα από τα παρακάτω σημεία:
• Πυώδες ή βλεννοπυώδες εξίδρωμα,
• Σχηματισμός εφελκίδων στις βλεφαρίδες
• Ερυθρότητα & πάχυνση των ελεύθερων βλεφαρικών χειλέων
• Απώλεια (άλλοτε άλλου βαθμού) βλεφαρίδων)
4. Ασθενείς που είναι πρόθυμοι και ικανοί να προσέλθουν σε ραντεβού της μελέτης εντός των επιτρεπόμενων χρονικών ορίων.
5. Ασθενείς που υπέγραψαν το Έντυπο Συγκατάθεσης μετά από Ενημέρωση.

E.4

Principal exclusion criteria

1. Patients aged <18 years
2. Patients who present with symptoms for more than 7 days
3. Patients with typical signs and/or symptoms of chlamydia, viral or fungal infection
4. Patients with an inflammation of allergic aetiology .
5. Patients with severe systemic infections
6. Patients receiving systemic antimicrobial treatment
7. Patients who underwent treatment with topical, ophthalmic antimicrobial or steroid medications during the last two weeks before their enrollment in the study.
8. Patients who underwent an ophthalmic surgery during the last 3 months before their enrollment in the study
9. Patients suffering from other ophthalmic diseases that may interfere with the outcomes of this study.
10. Patients with a history of severe allergy or known hypersensitivity to the study drugs or known hypersensitivity to any of the study drugs components, especially patients with a history of blood dyscrasias or patients who presented with bone marrow suppression following the administration of azidamfenicol eye drops solution
11. Pregnant of breast-feeding women.
12. Women of child-bearing potential who do not use adequate contraceptive measures.
13. Patients who, according the the investigator's opinion, are unlikely to comply with the study protocol or who are incapable to participate for any other reason or who do not wish to sign the Informed Consent form .

1. Aσθενείς ηλικίας <18 ετών
2. Ασθενείς που παρουσιάζουν συμπτώματα για περισσότερο από 7 ημέρες
3. Ασθενείς με τυπικά συμπτώματα ή /και σημεία λοίμωξης από χλαμύδια, ιό ή μύκητες
4. Ασθενείς που παρουσιάζουν φλεγμονή αλλεργικής αιτιολογίας.
5. Ασθενείς με σοβαρή συστηματική λοίμωξη
6. Ασθενείς που λαμβάνουν συστηματική αντιμικροβιακή θεραπεία
7. Ασθενείς που υποβλήθηκαν σε θεραπεία με οφθαλμικούς αντιμικροβιακούς παράγοντες ή με στεροειδή κατά τις τελευταίες δύο εβδομάδες πριν την ένταξή τους στη μελέτη.
8. Ασθενείς που υποβλήθηκαν σε χειρουργική επέμβαση στους οφθαλμούς κατά τους τελευταίους 3 μήνες πριν από την ένταξή τους στη μελέτη
9. Ασθενείς που πάσχουν από άλλες παθήσεις των οφθαλμών, που θα μπορούσαν να επηρεάσουν τις μεταβλητές της παρούσας μελέτης.
10. Ασθενείς με ιστορικό σοβαρής αλλεργίας ή υπερευαισθησίας σε σκευάσματα, είτε γνωστή υπερευαισθησία στα συστατικά των φαρμάκων της μελέτης και ειδικά ασθενείς που έχουν ιστορικό δυσκρασίας του αίματος ή ασθενείς που παρουσίασαν καταστολή του μυελού των οστών μετά από χορήγηση οφθαλμικών σταγόνων αζιθαμφαινικόλης
11. Γυναίκες ασθενείς που είναι έγκυες ή θηλάζουν.
12. Γυναίκες ασθενείς με ικανότητα τεκνοποίησης και που δεν χρησιμοποιούν επαρκή αντισύλληψη.
13. Ασθενείς που, κατά τη γνώμη του ερευνητή, είναι απίθανο να συμμορφωθούν με το πρωτόκολλο της κλινικής μελέτης ή δεν είναι κατάλληλοι για οποιουσδήποτε άλλους λόγους ή ασθενείς που δεν επιθυμούν να υπογράψουν το έντυπο συγκατάθεσης μετά από ενημέρωση.

E.5 End points

E.5.1

Primary end point(s)

Co-primary endpoints are:
- the assessment of the ophthalmic smear's culture (day 1 & 7), and
- the assessment of the bacterial conjuctivitis signes & symptoms grading system score (days 1, 3 & 7)

Συμπρωταρχικά καταληκτικά σημεία είναι:
- η αξιολόγηση της καλλιέργειας του οφθαλμικού επιχρίσματος (ημέρα 1 & 7), και
- η αξιολόγηση του συστήματος βαθμολογίας σημείων και συμπτωμάτων της βακτηριακής επιπεφυκίτιδας (ημέρα 1, 3 & 7).

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1, Day 3, Day 7

Hμέρα 1, Ημέρα 3, Ημέρα 7

E.5.2

Secondary end point(s)

The change in the score of the IGII scale (Investigator Global Improvement Index) and the change of the score of the PGII scale (Patient Global Improvement Index) (Day 7).

Η μεταβολή της βαθμολογίας της κλίμακας IGII (Investigator Global Improvement Index) και η μεταβολή της βαθμολογίας της κλίμακας PGII (Patient Global Improvement Index) (ημέρα 7).

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 7

Ημέρα 7

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

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

Τελευταία Επίσκεψη Τελευταίου Ασθενούς

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:

100

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

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)

Following completion of subject's participation in the study, if needed, the normal treatment practice for the microbial conjuctivitis are to be implemented

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

2013-05-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-03-19

P. End of Trial
P.	End of Trial Status	Ongoing

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