Clinical Trials Register

Summary
EudraCT Number:	2021-003387-27
Sponsor's Protocol Code Number:	848300145/0129/1POP04
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:	2021-09-03
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2021-003387-27

A.3

Full title of the trial

A PHASE III, MULTICENTRE, RANDOMISED, INVESTIGATOR-MASKED, CROSS-OVER, COMPARATIVE, NON-INFERIORITY TRIAL OF GENERIC LATANOPROST + TIMOLOL (50μG + 5MG)/ML EYE DROPS, SOLUTION (POLPHARMA S.A.) COMPARED TO XALACOM® (LATANOPROST 0.005 % OPHTHALMIC SOLUTION & TIMOLOL 0.5% FIXED COMBINATION, PFIZER) IN PATIENTS WITH OCULAR HYPERTENSION OR PRIMARY OPEN ANGLE GLAUCOMA.

A generikus latanoproszt + timolol (50 μg + 5 mg)/ml oldatos szemcsepp (Polpharma S.A.) és a Xalacom® (latanoproszt 0,005% és timolol 0,5% fix kombinációs 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

COMPARATIVE TRIAL OF GENERIC LATANOPROST + TIMOLOL (50μG + 5MG)/ML EYE DROPS, SOLUTION (POLPHARMA S.A.) COMPARED TO XALACOM® (LATANOPROST 0.005 % OPHTHALMIC SOLUTION & TIMOLOL 0.5% FIXED COMBINATION, PFIZER) IN PATIENTS WITH OCULAR HYPERTENSION OR PRIMARY OPEN ANGLE GLAUCOMA.

A generikus latanoproszt + timolol (50 μg + 5 mg)/ml oldatos szemcsepp (Polpharma S.A.) és a Xalacom® (latanoproszt 0,005% és timolol 0,5% fix kombinációs oldatos szemcsepp, Pfizer) összehasonlító vizsgálata emelkedett szembelnyomású vagy primer nyílt zugú glaucomában szenvedő betegeknél.

A.4.1

Sponsor's protocol code number

848300145/0129/1POP04

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	Pharmaceutical Works Polpharma S.A. (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	latanoprost + timolol (50 μg + 5 mg)/ml oldatos szemcsepp (Polpharma S.A.), 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	Ocular use Conjunctival use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Latanoprost and Timolol
D.3.9.1	CAS number	130209-82-4
D.3.9.3	Other descriptive name	LATANOPROST and Timolol
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	50
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	Xalacom®
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	Xalacom® (latanoproszt 0,005% és timolol 0,5% fix kombinációs oldatos szemcsepp, Pfizer).
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 is to evaluate the efficacy of the generic Latanoprost + Timolol (50μg + 5mg)/ml eye drops, solution (Polpharma S.A.; test product) in lowering IOP when compared to the originator Xalacom® (latanoprost 0.005% & timolol 0.5% fixed combination ophthalmic solution, Pfizer; reference product).

E.2.2

Secondary objectives of the trial

Secondary Objective(s)
• To compare the ocular tolerance of the test and reference products using an ocular comfort level score.
• To compare the levels of conjunctival hyperaemia 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 test product delivery device by comparison with the reference product delivery device.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

INCLUSION CRITERIA
• Ocular hypertension or primary open angle glaucoma in at least one eye: mean diurnal IOP measured on Day 1 before treatment at 8 am, 12 pm and 4 pm on the day must be higher than or equal to 22 mmHg, and lower than or equal to 34 mmHg (untreated, i.e. after washout).
• 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.
• No clinically significant or progressive retinal disease.
• No concomitant use of any topical ophthalmic medication other than artificial tears
• No ocular glucocorticoids in the previous 3 months
• No concomitant use of any medication that may increase adrenergic activity, i.e. psychotropic substances such as amitriptyline
• No systemic medication that may alter IOP in the previous 30 days (e.g. beta blockers, calcium channel blockers, ACE inhibitors, prostaglandins, etc.) or expected to continue the current treatment with these medicinal products on a stable regimen for the duration of the study.

Other inclusion criteria
• Age: 18-85 years old
• Provision of signed and dated Informed Consent.
• General health conditions not interfering with participation in the study determined e.g. by blood pressure, pulse rate and temperature at screening as assessed by the Investigator
• Female patients of childbearing potential should be either sexually inactive (abstinent) for 60 days prior to the first dose and throughout the study or be using acceptable methods of birth control.

E.4

Principal exclusion criteria

Exclusion Criteria
• Corrected visual acuity of less than 20/100 in both eyes
• Evidence of acute ocular infection, corneal foreign body, or ocular inflammation within 3 months of the screening visit.
• History or evidence of severe inflammatory eye disease (i.e. uveitis, retinitis, scleritis, iritis) in one or both eyes
• Previous significant ocular trauma, laser or incisional surgery within 3 months of the screening visit
• Traumatic cataract surgery with an open posterior capsule or any patient with an anterior chamber intraocular lens implant or aphakia
• IOP in either eye exceeding 34 mmHg (mean diurnal IOP on Day 1 before treatment at 8 am, 12 pm and 4 pm).
• Any corneal abnormalities preventing reliable applanation tonometry.
• Patients at risk of angle closure or evidence of acute, intermittent or chronic angle closure
• Forms of glaucoma resulting from conditions other than primary open-angle glaucoma or ocular hypertension, such as pigmentary or pseudo-exfoliative glaucoma.,
• Pupil with inadequate ability to dilate sufficiently for peripheral retinal examination.
• History or evidence of Herpes simplex keratitis.
• Patients with known risk factors for macular oedema.
• Patients suffering from reactive airway disease including bronchial asthma or with a history of bronchial asthma or severe chronic obstructive pulmonary disease.
• Patients suffering from Sinus bradycardia, sick sinus syndrome, sino-atrial block, second- or third-degree atrioventricular block not controlled with a pacemaker, overt cardiac failure, or cardiogenic shock.
• Patients, for which the absorption of the beta blocking agent, timolol, may in the Investigator’s opinion acerbate pre-existing systemic conditions, such as cardiac, vascular or respiratory disorders, hypoglycaemia or diabetes.
• Hypersensitivity to the active substances or to any of the excipients of the test or reference products.

E.5 End points

E.5.1

Primary end point(s)

PRIMARY ENDPOINT
Non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP in the study eye at baseline (measured at 8 am, 12 pm and 4 pm on the day before treatment initiation at 8 am the following day) on Day 1 and on Day 29 (before treatment at 8 am, and 4 and 8 hours after the first measurement. 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
Efficacy
Non-inferiority of the test product when compared to the reference product with respect to the differences in the mean IOP in the study eye at baseline for each of the three measurement time points before and after treatment.

Ocular Tolerance
• Difference between the investigational products with respect to ocular comfort level score at baseline (Day 1) and Day 29
• Difference between the investigational products with respect to conjunctival hyperaemia at baseline (Day 1) and Day 29.

Safety
• Difference between the investigational products with respect to general safety as assessed by vital signs and the incidence and nature of adverse events.

Usability
• Evaluation if usability of the test product delivery device by comparison with the reference product delivery device.

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

Xalacom

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.8.5.1

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

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.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

2021-11-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-03-22

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