Clinical Trials Register

Summary
EudraCT Number:	2011-003692-12
Sponsor's Protocol Code Number:	AZ02
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:	2012-01-10
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2011-003692-12

A.3

Full title of the trial

A phase III , multicentre, randomised, investigator-masked, cross-over, comparative efficacy study of a generic Brinzolamide 10 mg/ml ophthalmic suspension (Azad Pharma AG) and Brinzolamide 10 mg/ml ophthalmic suspendion (Azopt®, Alcon) in open-angle glaucoma and ocular hypertension patients.

A.3.1

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

The purpose of the study is to compare and evaluate the generic Brinzolamide ophthalmic suspension with a registered and marketed Brinzolamide ophthalmic suspension as a treatment for ocular hypertension and glaucoma

A.4.1

Sponsor's protocol code number

AZ02

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 Pharma 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	Appletree AG
B.5.2	Functional name of contact point	Clinical trial information
B.5.3	Address:
B.5.3.1	Street Address	Theaterstrasse 29
B.5.3.2	Town/ city	Winterthur
B.5.3.3	Post code	8401
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	0041522090640
B.5.5	Fax number	0041522090650
B.5.6	E-mail	georg.mathis@appletree-ag.ch

D. IMP Identification
D.IMP: 1
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	Azopt
D.2.1.1.2	Name of the Marketing Authorisation holder	Alcon
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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
D.3.4	Pharmaceutical form	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.3.9.4	EV Substance Code	SUB05892MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
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	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 generic
D.3.4	Pharmaceutical form	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.3.9.4	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.3.11 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

Patients suffering from open angle glaucoma and ocular hypertension with an elevated IOP, higher than 22mmHg and and lower or equal than 35 mmHg

E.1.1.1

Medical condition in easily understood language

Patients with an elevated ocular pressure in one ore both eye

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

The primary objective of this study is to evaluate the efficacy of Brinzolamide 10 mg/ml ophthalmic suspension (Azad Pharma AG) in lowering intraocular pressure (IOP) when compared to Azopt® ophthalmic suspension ( Brinzolamide Alcon,).

E.2.2

Secondary objectives of the trial

to compare the tolerance of the test and reference products using a global comfort level score.
to compare the levels of conjunctival hyperaemia induced by test and reference product
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

Ophthalmic inclusion criteria
1. Elevated IOP and open angles (irideocorneal angle >30 grad) in at least one eye: mean diurnal IOP measured at -12, -8, –4, -0 hours pre-treatment at Day 1 pre-treatment must be higher than 22 mmHg, and lower than or equal to 35 mmHg (untreated, i.e. after washout) in the study eye. If both eyes have the same IOP, the investigator will select the study eye, using a right, left assignment. Otherwise, the eye with higher IOP will be used for analysis.
2. 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.
3. In the previous 3 months no ocular trauma, surgery, inflammation or infection, no corneal foreign body
4. No clinically significant or progressive retinal disease
5. No concomitant use of any topical ophthalmic medication other than artificial tears
6. No ocular glucocorticoids in the previous 3 months
7. No concomitant use of any medication that may increase adrenergic activity, i.e. psychotropes such as amitriptyline
8. No systemic medication that may alter IOP in the previous 30 days (e.g. beta-blockers, Ca-channel-blockers, ACE-inhibitors, prostaglandins, etc.), or expected to continue the current treatment with these medicinal products on a stable regimen for 30 days prior to the study and during the study.
9. Patients may be contact lens wearers but must remove their contact lenses prior to each drug application and keep out the lenses for a minimum of 15 minutes after drug application. In addition contact lenses must remain out for a minimum of 20 minutes when ocular discomfort assessments are required. Contact lenses cannot be worn on days of visits to the clinic.

Other inclusion criteria:

10. Age 18 years or older
11. Passing the screening examination
12. Giving written Informed Consent
13. General health conditions not interfering with participation in the study e.g. blood pressure, pulse rate at screening will be assessed by the investigator
14. 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 one of the following acceptable methods of birth control:
i. Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum;
ii. IUD in place for at least 3 months;
iii. Barrier methods (condom, diaphragm) with spermicide for at least 60 days prior to the first dose and throughout the study;
iv. Hormonal contraceptives for at least 3 months prior to the first dose of the study
v. Postmenopausal women with amenorrhea for at least 2 years will be eligible

E.4

Principal exclusion criteria

Ophthalmic 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 within 3 months of the screening visit
3. Previous significant ocular trauma, laser or incisional surgery within 3 months of the screening visit
4. IOP in either eye exceeding 35 mmHg (mean diurnal at Day 1: -12, -8, –4, -0 hours)
5. Any corneal abnormalities preventing reliable applanation tonometry
6. Clinical significant or progressive retinal disease or retinal detachement;as determined by dilated peripheral retinal examination done at screening.
7. Patients with risk of angle closure or evidence of acute, intermittent or chronic angle closure
8. Types of glaucoma other than POAG (primary open-angle glaucoma) such as pigmentary or pseudo-exfoliative glaucoma
9. Pupil with inadequate ability to dilate sufficiently for peripheral retinal examination
10. History or evidence of severe inflammatory eye disease (i.e. uveitis, retinitis, scleritis) in one or both eyes
11. Traumatic cataract surgery with an open posterior capsule or any patient with an anterior chamber intraocular lens implant or aphakia

Other exclusion criteria
12. Pregnant or nursing women and women of childbearing potential not using adequate contraception. An urine pregnancy test will be administered to women of childbearing potential during screening, during the Day 1 visits of both treatment periods, and again at the end of the study; if the patient has a positive urine pregnancy a serum -hCG test will be performed for confirmation of pregnancy.
13. Confirmed positive test for pregnancy at medical screening or prior to dosing of either period
14. Patients who have participated in another research study for an investigational drug within 60 days of the screening visit
15. History of drug or alcohol abuse within the last 6 months
16. A history of sensitivity to 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 or renal impairment).
18. Patient with history of severe renal insufficiency (Creatinin Clearance <30ml/min) or hyperchloremic acidosis.
19. Hypertensivity to Brinzolamide and sulfonamides.

E.5 End points

E.5.1

Primary end point(s)

Difference between the Investigational Products with respect to the differences in the mean diurnal IOP in the study eye between baseline (pre-dose) and Day 29 (post dose).

E.5.1.1

Timepoint(s) of evaluation of this end point

After 14 and 29 days in both treatment ( Treatment Phase I and treatment Phase II)

E.5.2

Secondary end point(s)

Ocular Tolerance
oDifference between the test products and the reference products with respect to global comfort score at baseline (Day 1), Day 14 and 29.
Difference between the Investigational Products with respect to conjunctival hyperaemia at baseline (Day 1), Day 14 and 29

Safety
Difference between the Investigational Products with expect to general safety as assessed by occurrence of adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

Between Baseline and Day 29 on both Treatment (I and II)

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

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

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

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Azopt

comparator Product

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

when all patients have completed both treatment periods for both group (Azopt and Brinzolamide generic)

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

Yes

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.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)

AEs and SAEs existing of study end will be followed until the event is resolved, until the condition stabilises, until the event is otherwise explained (i.e. is assessed as not being Study Drug related), or until the patient is lost to follow up, but maximally for 30 days after study end.

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

2012-05-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-03-11

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