Clinical Trials Register

Summary
EudraCT Number:	2013-002066-39
Sponsor's Protocol Code Number:	REPEXStudy
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:	2013-07-10
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-002066-39

A.3

Full title of the trial

The Reggio Emilia study on bromfenac for patients with PseudoEXfoliation
syndrome undergoing cataract surgery: the REPEX study

Effetto del bromfenac collirio in pazienti con pseudoesfoliatio lentis sottoposti ad
intervento di cataratta

A.3.1

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

Evaluation of the anti-inflammatory effect of bromfenac eye drops after cataract
surgery in patients with pseudoexfoliatio of the lens

Valutazione dell'effetto anti-infiammatorio del collirio a base di bromfenac nei
pazienti operati di cataratta affetti dalla sindrome di pseudoesfoliazione del
cristallino

A.3.2

Name or abbreviated title of the trial where available

REPEX Study

A.4.1

Sponsor's protocol code number

REPEXStudy

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	Azienda Ospedaliera di Reggio Emilia Arcispedale "S.Maria Nuova"/IRCCS
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	Bausch & Lomb Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	A.O. di Reggio Emilia Arcispedale “S. Maria Nuova”/IRCCS
B.5.2	Functional name of contact point	Struttura Complessa di Oculistica
B.5.3	Address:
B.5.3.1	Street Address	Viale Risorgimento n. 80
B.5.3.2	Town/ city	Reggio Emilia
B.5.3.3	Post code	42123
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390522296219
B.5.5	Fax number	00390522295890
B.5.6	E-mail	marco.coassin@asmn.re.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	Yellox 0,9 mg/ml collirio
D.2.1.1.2	Name of the Marketing Authorisation holder	Croma Pharma GmbH (Austria)
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	Yellox 0.9 mg/ml collirio
D.3.4	Pharmaceutical form	Eye drops
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular 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.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	TOBRADEX 0,3% + 0,1% collirio sospensione
D.2.1.1.2	Name of the Marketing Authorisation holder	S.A. ALCON Couvreur N.V., 2870 PUURS (Belgio)
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	TOBRADEX 0,3% + 0,1% collirio
D.3.4	Pharmaceutical form	Eye drops
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular 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

Postoperative inflammation in patients with pseudoexfoliatio lentis undergoing cataract
surgery

Infiammazione oculare dopo intervento di cataratta in soggetti affetti da
pseudoesfoliatio lentis

E.1.1.1

Medical condition in easily understood language

Patients enrolled in the study have “fragile” eyes due to an idiopatic condition called
pseudoexfoliatio lentis and characterized by white deposits on the surface of the
crystalline lens.

I soggetti hanno occhi particolarmente fragili a causa di una
condizione idiopatica che si manifesta con depositi biancastri sulla superficie del
cristallino che sembra come si stesse esfoliando.

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

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 bromfenac ophthalmic solution 0.09% for reducing
postoperative inflammation in eyes with pseudoexfoliation syndrome (PEX) undergoing
cataract surgery and receiving standard postoperative eye drops (dexamethasone
0.1% plus tobramycin 0.3% ophthalmic solution).

Questo studio intende provare che l’aggiunta di un FANS in
collirio (il bromfenac) alla terapia antibiotico-steroidea standard è in grado di migliorare
i risultati della chirurgia della cataratta, in particolare in occhi proni alle complicanze
intraoperatorie e postoperatorie come quelli con sindrome da pseudoesfoliazione.

E.2.2

Secondary objectives of the trial

In particular, our study is intended to demonstrate:
1) a reduction in the anterior segment inflammation in PEX eyes treated with standard
regimen plus bromfenac when compared to the standard treatment only. Anterior
chamber inflammation will be measured with the Laser Flare Photometer.
2) a reduction in the posterior segment inflammation and incidence of macular edema
in PEX eyes treated with standard regimen plus bromfenac when compared to the
standard treatment only. Macular thickness will be measured with the OCT.

In particolare, intende dimostrare che:
1) l’infiammazione postoperatoria nella camera anteriore dell’occhio con PEX operato di
cataratta è minore negli occhi trattati anche con bromfenac collirio rispetto a quelli
trattati solo con la terapia cortisonica standard. L’infiammazione verrà misurata con il
Laser Flare Photometer, un nuovo metodo per quantificare precisamente la reazione
flogistica nel segmento anteriore dell’occhio.
2) l’infiammazione postoperatoria nel segmento posteriore dell’occhio, e di
conseguenza l’incidenza di edema maculare cistoide, è minore negli occhi trattati anche
con bromfenac collirio rispetto a quelli trattati solo con la terapia cortisonica standard.
L’infarcimento della regione maculare verrà misurato con il Tomografo a coerenza
ottica ad alta definizione (Spectral Domain OCT), una nuova tecnica per visualizzare e
quantificare precisamente la presenza di edema maculare.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients with cataract:
- with nuclear sclerosis of the crystalline lens graded 1 or more according to the LOCS
II classification (Lens opacities classification system II; Chylack LT et al. 1989);
- with classics sign of pseudoesfoliatio lentis (PEX).
The diagnosis of PEX will be made by demonstrating the pathognomonic white deposits
in the lens, cornea, iris and anterior hyaloid face by slit lamp examination.

Occhi con cataratta senile e segni classici di pseudoesfoliatio lentis (PEX) saranno
inclusi nello studio. Solo occhi con cataratta senile con opacità nucleare di grado 1 o
superiore verranno inclusi nello studio, in base alla classificazione LOCS II (Lens
opacities classification system II; Chylack LT et al. 1989). La diagnosi di PEX verra’
fatta mediante la dimostrazione della presenza dei depositi biancastri patognomonici
sul cristallino, la cornea, l’iride e la ialoide anteriore mediante esame alla lampada a
fessura.

E.4

Principal exclusion criteria

Patients with history of ocular inflammation or trauma, previous intraocular surgery,
corneal haze, retinal vascular disease, diabetic retinopathy, variation of the foveal
profile at OCT (including macular edema and epiretinal membrane), moderate to
severe age related macular degeneration or age < 60 year will be excluded. Only one
eye per patient will be included in our study.

Pazienti con storia di infiammazioni oculari o trauma, pregressa chirurgia intraoculare,
opacita’ corneali, malattie vascolari retiniche o retinopatia diabetica, edema maculare,
membrana epiretinica, degenerazione maculare senile di grado moderato o severo, eta’
inferiore ai 60 anni. Un solo occhio per paziente potrà essere incluso nello studio.

E.5 End points

E.5.1

Primary end point(s)

Reduction of 30% of anterior chamber inflammation evaluated by Laser Flare
Photometry (LFP) in the bromfenac arm when compared to the non-bromfenac arm at
postoperative day 3. LFP is a new, non invasive, objective method to measure ocular
inflammation.

Riduzione dell’infiammazione in
camera anteriore dell’occhio del 30% nel gruppo trattato con bromfenac rispetto al
gruppo non trattato in corrispondenza della terza giornata postoperatoria. La
valutazione dell’infiammazione verrà effettuata con Laser Flare Photometry.

E.5.1.1

Timepoint(s) of evaluation of this end point

Third postoperative day

Terza giornata postoperatoria

E.5.2

Secondary end point(s)

1) Macular thickness: proportion of patients with central macular thickness greater
than 300 microns at week 4.
2) Best corrected visual acuity (BCVA): proportion of subjects with BCVA equal to
10/10 at week 1.
3) Ocular discomfort: proportion of patients who had no ocular pain at day 3, evaluated
by OCGA questionnaire (the Ocular Comfort Grading Assessment measures 7 ocular
symptoms: eye pain, tearing, itching, foreign body sensation, photophobia, eye
discharge, and haziness).

1) Proporzione di pazienti con spessore maculare maggiore di 300 microns misurato
con OCT a 4 settimane
2) Proporzione di pazienti con acuità visiva (con correzione) inferiore a 10/10 ad una
settimana
3) Discomfort oculare: proporzione di pazienti con assenza di dolore al giorno 3 rilevata
mediante somministrazione del questionario OCGA (Ocular Comfort Grading
Assessment: rileva sintomi oculari quali dolore, bruciore, lacrimazione, sensazione di
corpo estraneo, fotofobia, secrezione, offuscamento).

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Week 4
2) Week 1
3) Postoperative day 3

1) Quattro settimane
2) Una settimana
3) Terza giornata postoperatoria

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

E.6.5

Efficacy

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

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.8.5

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 = last patient last treatment

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

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

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)

After the end of the study, the assistance to the participants will be guaranteed at any
time by the ophthalmologists of the Department of Ophthalmology through the
Emergency Room of the Arcispedale Santa Maria Nuova, Reggio Emilia (in the same way
of the other patients not included in the study who routinely undergo a cataract surgery
in our hospital).

I partecipanti allo studio, successivamente al completamento dello stesso, potranno
accedere in qualsiasi momento all’assistenza garantita dai medici oculisti della S.C. di
Oculistica tramite il Pronto Soccorso dell’Arcispedale Santa Maria Nuova di Reggio Emilia
in modo del tutto analogo agli altri pazienti non inclusi nello studio che routinariamente
vengo operati di cataratta nella nostra struttura.

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

2013-09-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-17

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials