Clinical Trials Register

Summary
EudraCT Number:	2010-024512-34
Sponsor's Protocol Code Number:	C-10-040
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:	2011-04-19
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

2010-024512-34

A.3

Full title of the trial

Safety and IOP-Lowering Efficacy of Brinzolamide 10 mg/ml / Brimonidine 2 mg/ml Fixed Combination Eye Drops, Suspension compared to Brinzolamide 10 mg/ml Eye Drops, Suspension and Brimonidine 2 mg/ml Eye Drops, Solution in Patients with Open-Angle Glaucoma or Ocular Hypertension

A.3.1

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

Safety and eye pressure lowering effect of Brinz/Brim eye drops , compared to Brinzolamide and Brimonidine given separately in patients with increased eye pressure (ocular hypertension) or with associated changes to the nerve inside the eye (glaucoma).

A.3.2

Name or abbreviated title of the trial where available

Brinz/Brim BID FC vs Brinzolamide BID and Brimonidine BID in Patients with OAG

A.4.1

Sponsor's protocol code number

C-10-040

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01310777

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	Alcon Research, Ltd.
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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 10 mg/ml/Brimonidine Tartrate 2 mg/ml Eye Drops, Suspension
D.3.2	Product code	115576
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	Topical use (Noncurrent) 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.3.10	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	BRIMONIDINE TARTRATE
D.3.9.1	CAS number	79570-19-7
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	2
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	AZOPT
D.2.1.1.2	Name of the Marketing Authorisation holder	Alcon Laboratories (UK), 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.3.1	Product name	Brinzolamide 10 mg/ml Eye Drops, Suspension
D.3.2	Product code	89984
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	Topical use (Noncurrent) 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.3.10	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.IMP: 3
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	Information not present in EudraCT
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	Brimonidine Tartrate 2 mg/ml Eye Drops, Solution
D.3.2	Product code	101461
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	Topical use (Noncurrent) Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BRIMONIDINE TARTRATE
D.3.9.1	CAS number	79570-19-7
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	2
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

Open-angle glaucoma and ocular hypertension

E.1.1.1

Medical condition in easily understood language

Elevated pressure in the eye with (glaucoma) or without optic nerve damages (ocular hypertension)

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	13.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Brinzolamide 10 mg/mL / brimonidine 2 mg/mL eye drops,
suspension is superior to brinzolamide 10 mg/mL eye drops,
suspension, with respect to IOP-lowering efficacy, and
brinzolamide 10 mg/mL / brimonidine 2 mg/mL eye drops,
suspension is superior to brimonidine 2 mg/mL eye drops,
solution, with respect to IOP-lowering efficacy

E.2.2

Secondary objectives of the trial

There are no secondary objectives.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients 18 years of age or older, of either gender, and any
race/ethnicity, diagnosed with open angle glaucoma or ocular
hypertension, who in the opinion of the Investigator are
insufficiently controlled on monotherapy or are already on
multiple IOP-lowering medications.
2. Patients should be able to understand and sign an informed
consent that has been approved by an Institutional Review
Board/Independent Ethics Committee.
3. Mean IOP measurements in at least 1 eye, the same eye(s),
must be:
• ≥ 24 mmHg and ≤ 36 mmHg at the 9 AM time point
and,
• ≥ 21 mmHg and ≤ 36 mmHg at the 11 AM time point at
both E1 and E2 Visits.
IOP must not be > 36 mmHg at any time point.

E.4

Principal exclusion criteria

1. Females of childbearing potential (those who are not surgically
sterilized or post-menopausal for at least 1 year) are excluded
from participation in the studyif they meet any one of the
following conditions:
a. are currently pregnant or,
b. have a positive result on the urine pregnancy test at the
Screening Visit or,
c. intend to become pregnant during the study period or,
d. are breast-feeding or,
e. they are not using highly effective birth control measures,
such as:
Hormonal –
oral, implanted, transdermal, or injected
contraceptives;
Mechanical –
spermicide in conjunction with a barrier such
as a condom or diaphragm or IUD.
Patients with Schaffer angle Grade < 2, as measured by
gonioscopy (extreme narrow angle with complete or partial
closure).
3. Patients with a cup/disc ratio (C/D) greater than 0.80
(horizontal or vertical measurement).
4. Patients with severe central visual field loss. Severe central
visual field loss is defined as a sensitivity of less than or equal
to 10 dB in at least 2 of the 4 visual field test points closest to
the point of fixation.
5. Patients who cannot safely discontinue use of all IOPlowering
ocular medication(s) for a minimum period of 5 days
± 1 day to 28 days ± 1 day prior to Eligibility 1 (E1) Visit.
Chronic, recurrent or severe inflammatory eye disease
(ie, scleritis, uveitis, herpes keratitis).
7. Ocular trauma within the past 6 months.
8. Ocular infection or ocular inflammation within the past 3
months.
9. Clinically significant or progressive retinal disease such as
retinal degeneration, diabetic retinopathy, or retinal
detachment.
10. Best-corrected visual acuity (BCVA) score worse than 55
ETDRS letters (equivalent to approximately 20/80 Snellen,
0.60 logMAR, or 0.25 decimal).
11. Other ocular pathology (including severe dry eye) that may, in
the opinion of the Investigator, preclude the administration of
alpha-adrenergic agonist and/or topical carbonic anhydrase
inhibitor (CAI).
12. Intraocular surgery within the past 6 months.
13. Ocular laser surgery within the past 3 months.
14. Any abnormality preventing reliable applanation tonometry.
15. Any other conditions including severe illness which would
make the patient, in the opinion of the Investigator, unsuitable
for the study.
16. History of active, severe, unstable or uncontrolled
cardiovascular (eg, coronary insufficiency, hypertension,
Raynaud’s phenomenon, orthostatic hypotension,
thromboangiitis obliterans), cerebrovascular (eg, cerebral
insufficiency), hepatic, or renal disease that would preclude
the safe administration of a topical alpha-adrenergic agonist or
CAI in the opinion of the investigator.
17. Patients with recent (within 4 weeks of the Eligibility 1 Visit)
use of high-dose (> 1 g daily) salicylate therapy.
18. Current or anticipated treatment with any psychotropic drugs
that augment adrenergic response (eg, desipramine,
amitriptyline).
19. Concurrent use of monoamine oxidase inhibitor.
20. Therapy with another investigational agent within 30 days
prior to the Screening Visit.
21. Hypersensitivity to alpha-adrenergic agonist drugs, topical or
oral CAIs, sulfonamide derivatives, or to any component of
the study medications in the opinion of the Investigator.
22. Less than 30 days stable dosing regimen before the Screening
Visit of any medications or substances administered by any
route and used on a chronic basis that may affect IOP,
including but not limited to, β-adrenergic blocking agents.
23. Use of any additional topical or systemic ocular hypotensive
medication during the study.
24. Concurrent use of glucocorticoids administered by any route.

E.5 End points

E.5.1

Primary end point(s)

Primary:
• Mean diurnal IOP change from baseline (Month 3).
Supportive Efficacy:
• Diurnal IOP change from baseline (Week 2, Week 6)
• IOP (Week 2, Week 6, Month 3)
• IOP change from baseline (Week 2, Week 6, Month 3)
• IOP % change from baseline (Week 2, Week 6, Month 3)
• Percentage of patients with IOP < 18 mmHg at each ontherapy
visit and time point (Week 2, Week 6, Month 3).)
Safety: Pachymetry, fundus parameters, BCVA, slit-lamp exam,
standard automated perimetry, pulse / blood pressure,
Gonioscopy, adverse events.

E.5.1.1

Timepoint(s) of evaluation of this end point

Average other 9 AM + 2Hrs, + 7Hrs and + 10 Hrs (this last time point will be collected at only same selected sites.

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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

E.8.1.4

Double blind

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Germany

Hungary

Italy

Latvia

Lithuania

Mexico

New Zealand

Portugal

Singapore

Spain

Taiwan

Thailand

United Kingdom

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