Clinical Trials Register

Summary
EudraCT Number:	2018-001727-39
Sponsor's Protocol Code Number:	POP03
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-08-14
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2018-001727-39

A.3

Full title of the trial

A PHASE III, MULTICENTRE, RANDOMISED, INVESTIGATOR-MASKED, CROSSOVER,
COMPARATIVE, NON-INFERIORITY TRIAL EVALUATING THE EFFICACY
AND TOLERABILITY OF GENERIC LATANOPROST 0.05 MG/ML EYE DROPS
SOLUTION (POLPHARMA S.A.) COMPARED TO XALATAN® (LATANOPROST 0.005
% OPHTHALMIC SOLUTION, PFIZER) IN PATIENTS WITH OCULAR
HYPERTENSION OR PRIMARY OPEN ANGLE GLAUCOMA.

A generikus latanoprost 0,05 mg/ml oldatos szemcsepp (Polpharma S.A.) és a Xalatan® (latanoprost 0,005 % oldatos szemcsepp, Pfizer) III. fázisú, multicentrikus, randomizált, a vizsgáló előtt maszkolt, keresztezett, összehasonlító, non-inferioritási vizsgálata emelkedett szembelnyomású vagy primer nyílt zugú glaucomában szenvedő betegeknél.

A.3.1

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

EFFICACY AND TOLERABILITY OF GENERIC LATANOPROST 0.05 MG/ML EYE DROPS
SOLUTION (POLPHARMA S.A.) COMPARED TO XALATAN® (LATANOPROST 0.005
% OPHTHALMIC SOLUTION, PFIZER) IN PATIENTS WITH OCULAR
HYPERTENSION OR PRIMARY OPEN ANGLE GLAUCOMA.

A generikus latanoprost 0,05 mg/ml oldatos szemcsepp (Polpharma S.A.) és a Xalatan® (latanoprost 0,005 % oldatos szemcsepp, Pfizer) összehasonlító vizsgálata emelkedett szembelnyomású vagy primer nyílt zugú glaucomában szenvedő betegeknél.

A.4.1

Sponsor's protocol code number

POP03

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	Polpharma S.A.
B.1.3.4	Country	Poland
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	Polpharma S.A.
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Appletree CIG-AG
B.5.2	Functional name of contact point	Eva Szucs
B.5.3	Address:
B.5.3.1	Street Address	Sport u.3.
B.5.3.2	Town/ city	Budapest
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+36702450085
B.5.6	E-mail	e.szucs@appletree-cig.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	generic latanoprost 0.5 mg/mL, preservative free
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	Conjunctival use (Noncurrent) Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Latanoprost
D.3.9.1	CAS number	130209-82-4
D.3.9.3	Other descriptive name	LATANOPROST
D.3.9.4	EV Substance Code	SUB08409MIG
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	0.5
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	Xalatan®
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	Hungary
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	Xalatan® (Latanoprost 0.005% ophthalmic solution)
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	Conjunctival use (Noncurrent)
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

Ocular hypertension and open angle glaucoma

E.1.1.1

Medical condition in easily understood language

glaucoma

zöldhályog

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10030043
E.1.2	Term	Ocular hypertension
E.1.2	System Organ Class	10015919 - Eye disorders

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	10030348
E.1.2	Term	Open angle glaucoma
E.1.2	System Organ Class	10015919 - Eye 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

PRIMARY OBJECTIVE
The primary objective of this study is to evaluate the efficacy and tolerability of Latanoprost
Polpharma (test product) in lowering of IOP when compared to the originator Xalatan®
(reference product).

E.2.2

Secondary objectives of the trial

SECONDARY OBJECTIVES
The secondary objectives of this study are:
 To compare the ocular tolerance of the test and reference products using an ocular
comfort level score.
 To compare the levels of conjunctival hyperemia induced by test product and reference
product.
 To evaluate safety in general determined by vital signs and the incidence and nature of
AEs of the test product compared to the reference product.
 To evaluate the usability of the newly developed delivery device (newly developed
dropper bottle) in a subgroup of the patients.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

INCLUSION CRITERIA
A patient is eligible for inclusion in this study if all of the following criteria apply.
5.2.1.1 Inclusion Criteria
1. Male or female patients, 18-75 years old.
2. Provision of signed and dated Informed Consent.
3. General health conditions not interfering with participation in the study e.g.
blood pressure, pulse rate at screening as assessed by the investigator.
4. A female patient meeting one of the following criteria:
4.1. Participant is of childbearing potential and agrees to use one of the accepted
contraceptive regimens from at least 28 days prior to the first study drug
administration through to at least 30 days after the last dose of the study drug. An
acceptable method of contraception includes one of the following:
 Abstinence from heterosexual intercourse;
 Systemic contraceptives (combined birth control pills,
injectable/implant/insertable hormonal birth control products, transdermal
patch);
 Intrauterine device (IUD) (with or without hormones);
 Male condom with spermicide or male condom with a vaginal spermicide (gel,
foam, or suppository);
 Male partner vasectomized at least 6 months prior to the first study drug
administration;
Or
4.2. Participant whose partner has had a vasectomy less than 6 months prior to dosing,
and agrees to use an additional acceptable method of contraception from the first
study drug administration through to at least 30 days after the last dose of the study
drug.
Or
4.3. Participant is of non-childbearing potential, defined as surgically sterile (i.e. has
undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is
in a postmenopausal state (i.e. at least 1 year without menses prior to the first study
drug administration).
5. Ocular hypertension or primary open angle glaucoma in at least one eye: mean diurnal
IOP measured at -12, -8, –4, 0 hours pre-treatment on Day 1 must be higher than or
equal to 22 mmHg, and lower than or equal to 34 mmHg (naïve or untreated, i.e. after
washout). The eye with the higher IOP will be selected as the study eye. If both eyes
have the same IOP, the right eye will be selected.
6. Not on any ophthalmic pressure-lowering medication, or able to be withdrawn from
current pressure-lowering medications for the washout periods as defined in this
clinical trial protocol.
7. No ocular trauma, surgery, inflammation or infection, no corneal foreign body in
the previous 3 months.
8. No clinically significant or progressive retinal disease as determined by dilated
peripheral retinal examination done at screening.
9. No concomitant use of any topical ophthalmic medication other than artificial tears.
10. No ocular glucocorticoids in the previous 3 months.
11. Within the previous 30 days prior to the first dose (visit 1) no systemic medication
that may alter IOP (e.g. beta blockers, calcium channel blockers, ACE inhibitors,
prostaglandins, etc.) unless the current treatment with these medicinal products
continues on a stable regimen for the duration of the study.
12. Patients may be contact lens wearers but must remove their contact lenses prior to
each drug application and keep them removed for a minimum of 15 minutes after
drug application. In addition, contact lenses must remain removed for a minimum of
20 minutes when ocular discomfort assessments are required. Contact lenses cannot
be worn on the days of visits to the clinic.

E.4

Principal exclusion criteria

Exclusion Criteria
1. Corrected visual acuity of less than distance Snellen 20/100 corresponding to decimal 0.20
or logMAR 0.70 in both eyes.
2. Evidence of acute ocular infection, corneal foreign body, or ocular inflammation within 3
months of the screening visit.
3. History or evidence of severe inflammatory eye disease (i.e. uveitis, retinitis, scleritis,
iritis) in one or both eyes
4. Previous significant ocular trauma, laser or incisional surgery within 3 months of the
screening visit including cataract surgery.
5. Traumatic cataract surgery with an open posterior capsule or any patient with an anterior
chamber intraocular lens implant or aphakia
6. IOP in either eye greater than 34 mmHg at Day 1 (mean diurnal IOP measured at -12, -8, –
4, 0 hours pre-treatment)
7. Any corneal abnormalities preventing reliable applanation tonometry.
8. Patients at risk of angle closure or evidence of acute, intermittent or chronic angle closure.
9. Patients with forms of glaucoma resulting from conditions other than primary open angle
glaucoma, such as pigmentary or pseudo-exfoliative glaucoma, open angle glaucoma of
pseudophakic patients, neovascular glaucoma.
10. Pupil with inadequate ability to dilate sufficiently for peripheral retinal examination.
11. History or evidence of Herpes simplex keratitis.
12. Patients with known risk factors for macular edema.
13. Pregnant or nursing women or women who intend to become pregnant during the trial.
14. Patients who have participated in another research study for an investigational product or
investigational medical device within 30 days of the screening visit.
15. History of drug or alcohol abuse within the last 6 months.
16. A history of hypersensitivity to latanoprost, or any component in the formulation of the
products being tested.
17. History of evidence of any medical condition that would, in the opinion of the investigator,
make the patient unsuitable for the study (i.e. severe hepatic, cardiovascular or renal
impairment).
18. Systemic medication that may alter IOP in the previous 30 days (i.e. beta-blockers, calcium
channel blockers, angiotensin converting enzyme (ACE) inhibitors, prostaglandins etc.) if
the treatment regimen with these medicinal products is change during the study.

E.5 End points

E.5.1

Primary end point(s)

PRIMARY ENDPOINT
Non-inferiority of test product when compared with reference product, with respect to the
differences in the mean diurnal IOP in the study eye at baseline (measured at -12, -8, -4 and
0 hours before treatment) on Day 1 and Day 29 (12, 16, 20 and 24 hours after treatment the
previous day). IOP will be assessed using the Goldmann applanation tonometry.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day1 versus Day29

E.5.2

Secondary end point(s)

SECONDARY ENDPOINTS
• Ocular Tolerance
o Difference between the investigational products with respect to ocular comfort level
score at baseline (Day 1) and Day 29.
o Difference between the investigational products with respect to conjunctival
hyperemia at baseline (Day 1) and Day 29.
• Safety
o Difference between the investigational products with respect to general safety as
assessed by vital signs and the incidence and nature of adverse events.
• Usability
o Evaluation if usability of each of the delivery devices by the patients.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 1 vs Day 29

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)

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

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

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.8.2.3.1

Comparator description

Xalatan

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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)

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.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)

Treatment as per standard of care.

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

2018-10-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-03-13

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