Clinical Trials Register

Summary
EudraCT Number:	2016-000946-69
Sponsor's Protocol Code Number:	AZ07
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-07-01
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2016-000946-69

A.3

Full title of the trial

A PHASE III, MULTICENTRE, RANDOMISED, INVESTIGATOR-MASKED, CROSS- OVER, COMPARATIVE CLINICAL TRIAL EVALUATING THE EFFICACY AND SAFETY OF THE GENERIC BRINZOLAMIDE 10 MG/ML + TIMOLOL 5 MG/ML EYE DROPS SUSPENSION (AZAD PHARMA AG) WITH BRINZOLAMIDE 10 MG/ML + TIMOLOL 5 MG/ML EYE DROPS SUSPENSION AZARGA® (ALCON LTD) IN OPEN- ANGLE GLAUCOMA AND OCULAR HYPERTENSION PATIENTS

Wieloośrodkowe, randomizowane, zaślepione dla badacza, krzyżowe, porównawcze badanie kliniczne III fazy oceniające skuteczność i bezpieczeństwo generycznego produktu brinzolamide 10 mg/ml + timolol 5 mg/ml (Azad Pharma AG) w postaci zawiesiny kropli do oczu z brinzolamide 10 mg/ml + timolol 5 mg/ml w postaci zawiesiny kropli do oczu Azarga ® (Alcon Ltd ) u pacjentów z jaskrą z otwartym kątem przesączania i nadciśnieniem wewnątrzgałkowym.

A.3.1

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

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative clinical trial evaluating the efficacy and safety of the generic Brinzolamide 10 mg/ml + Timolol 5 mg/ml eye drops suspension (AZAD Pharma AG) and of Brinzolamide 10 mg/ml + Timolol 5 mg/ml eye drops suspension Azarga® (Alcon Ltd) in open-angle glaucoma and ocular hypertension patients

A.3.2

Name or abbreviated title of the trial where available

Azad Brinolamid/Timolol combination generic study

A.4.1

Sponsor's protocol code number

AZ07

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	AZAD Pharma AG
B.1.3.4	Country	Switzerland
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	Azad AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Azad AG
B.5.2	Functional name of contact point	Van Van Khov
B.5.3	Address:
B.5.3.1	Street Address	Bahnhofstrasse 9
B.5.3.2	Town/ city	Toffen
B.5.3.3	Post code	CH-3125
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	004152632 09 2323
B.5.5	Fax number	004152632 09 1111
B.5.6	E-mail	vkhov@azad.ch

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	Brinzolamide 10mg/ml + Timolol 5mg/ml
D.3.2	Product code	Brinzolamide 10mg/ml + Timolol 5mg/ml
D.3.4	Pharmaceutical form	Ear/eye drops, suspension
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	Brinzolamide
D.3.9.1	CAS number	138890-62-7
D.3.9.3	Other descriptive name	BRINZOLAMIDE
D.3.9.4	EV Substance Code	SUB05892MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Timolol maleate
D.3.9.1	CAS number	26921-17-5
D.3.9.3	Other descriptive name	TIMOLOL
D.3.9.4	EV Substance Code	SUB11069MIG
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	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	Azarga®
D.2.1.1.2	Name of the Marketing Authorisation holder	Alcon Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Ear/eye drops, suspension
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	Brinzolamide
D.3.9.1	CAS number	138890-62-7
D.3.9.3	Other descriptive name	BRINZOLAMIDE
D.3.9.4	EV Substance Code	SUB05892MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Timolol maleate
D.3.9.1	CAS number	26921-17-5
D.3.9.3	Other descriptive name	TIMOLOL
D.3.9.4	EV Substance Code	SUB11069MIG
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	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.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

Decrease of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction

E.1.1.1

Medical condition in easily understood language

Decrease of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom monotherapy provides insufficient IOP reduction

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	19.0
E.1.2	Level	HLGT
E.1.2	Classification code	10018307
E.1.2	Term	Glaucoma and ocular hypertension
E.1.2	System Organ Class	10015919 - Eye disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the efficacy of the generic Brinzolamide 10
mg/ml + Timolol 5 mg/ml eye drops suspension AZAD Pharma AG (test product) in lowering
intra-ocular pressure (IOP) when compared to Brinzolamide 10 mg/ml + Timolol 5mg/ml eye
drops suspension product Azarga® (reference product, Alcon Ltd).

E.2.2

Secondary objectives of the trial

1. To compare the tolerance of the test and reference products using a ocular comfort level
score.
2. To compare the levels of conjunctival hyperaemia induced by test product and reference
product.
3. To evaluate the general safety of the test product compared to the reference product.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Elevated IOP / primary open angle glaucoma (irideocorneal angle > 30°) in at least one
eye: IOP pre-treatment (measured at approx. 8 am, 10 am and 4 pm) must be equal or
higher than 22 mmHg, and equal or lower to 35 mmHg (untreated, i.e. naïve or after
washout).

2. Not on any ophthalmic pressure-lowering medication, or in the condition not to suffer
an untoward effects by withdrawal from current pressure-lowering medications for the
washout period(s).

3. No ocular trauma, surgery, inflammation or infection, no corneal foreign body in the
previous 3 months.

4. No clinically significant or progressive retinal disease as determined by dilated
peripheral retinal examination done at screening.

5. No concomitant use of any topical ophthalmic medication other than artificial tears.

6. No ocular glucocorticoids in the previous 3 months.

E.4

Principal exclusion criteria

1. Visual acuity of less than distance Snellen 20/100 corresponding to decimal 0.20 or 0.70
logMAR in either eye.

2. Evidence of acute ocular infection, corneal foreign body, or ocular inflammation.

3. Previous significant ocular trauma, laser or incisional surgery within 3 months of the
screening visit.

4. Any corneal abnormalities preventing reliable applanation tonometry.

5. Patients with risk of angle closure or evidence of acute, intermittent or chronic angle
closure.

6. Types of glaucoma other than POAG with glaucomatous optic disc morphology or
glaucoma visual field defect such as pigmentary or pseudo-exfoliative glaucoma.

7. Pupil with inadequate ability to dilate sufficiently for peripheral retinal examination.

8. History or evidence of severe inflammatory eye disease (i.e. uveitis, retinitis, scleritis) in
one or both eyes.

9. Traumatic cataract surgery with an open posterior capsule or any patient with an anterior
chamber intraocular lens implant or aphakia

10. Pregnant or nursing women.

11. History of drug or alcohol abuse within the last 6 months.

12. A history of hypersensitivity to Brinzolamide, Timolol, sulphonamides or any component
in the formulation of the products being tested.

13. Patient with history of severe renal insufficiency (Creatinin Clearance <30ml/min) or
hyperchloremic acidosis.

14. Patients with reactive airway disease including bronchial asthma or a history of bronchial
asthma, or severe chronic obstructive pulmonary disease.

15. Patients with sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third
degree atrioventricular block not controlled with pace-maker. Overt cardiac failure,
cardiogenic shock.

16. Patients with severe allergic rhinitis.

17. Patients who have participated in another research study for an investigational drug within
30 days of the screening visit.

18. History of evidence of any medical condition that would, in the opinion of the investigator,
make the patient unsuitable for the study.

19. 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.) or not expected to continue the current treatment with these medical products on a stable
regimen for 30 days prior to the study and during the study.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is non-inferiority of test product when compared with reference product, with respect to the differences in the mean diurnal IOP measured at approximately 8 am, 10 am and 4 pm in the
study eye between Day 1 (baseline, before treatment) and Day 22 (under treatment).

E.5.1.1

Timepoint(s) of evaluation of this end point

Diurnal IOP measured at approximately 8 am, 10 am and 4 pm in the
study eye between Day 1 (baseline, before treatment) and Day 22 (under treatment).

E.5.2

Secondary end point(s)

a) Ocular tolerance:
- Difference between the investigational products with respect to ocular comfort score at baseline Day 1 and Day 22
- Difference between investigational products with respect to conjunctival hyperaemia at baseline Day 1 and Day 22

b) Safety:
Difference between investigational products with respect to general safety as assessed by occurence of adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 1 (baseline) and Day 22 (under treatment)

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.8.2.4

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

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

End of trial is Las Visit of Last Subject 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

2016-10-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-05-18

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