Clinical Trials Register

Summary
EudraCT Number:	2010-024512-34
Sponsor's Protocol Code Number:	C-10-040
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-01
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

Spain - AEMPS

A.2

EudraCT number

2010-024512-34

A.3

Full title of the trial

Seguridad y eficacia en la reducción de la presión intraocular de gotas oculares de combinación fija de brinzolamida 10 mg/ml / brimonidina 2 mg/ml, suspensión en comparación con gotas oculares de brinzolamida de 10 mg/ml, suspensión y gotas oculares de Brimonidina 2 mg/ml, solución, en pacientes con glaucoma de ángulo abierto o hipertensión ocular / 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

Seguridad y eficacia en la reducción de la presión intraocular de BrinzBrim en comparación con brinzolamida y brimonidina dadas por separado en pacientes con hipertensión ocular o con cambios en el nervio del ojo (glaucoma) /Safety and eye pressure lowering effect of Brinz/Brim, compared to Brinzolamide and Brimonidine given separately in patients with 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

A.4.1

Sponsor's protocol code number

C-10-040

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	Alcon Research, Ltd.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Alcon Cusí S.A.
B.5.2	Functional name of contact point	Elena Simo
B.5.3	Address:
B.5.3.1	Street Address	C/camil Fabra 58
B.5.3.2	Town/ city	El Masnou - Barcelona
B.5.3.3	Post code	08320
B.5.3.4	Country	United States
B.5.4	Telephone number	934977013
B.5.5	Fax number	934977023
B.5.6	E-mail	elena.simo@alconlabs.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	Brinzolamida 10 mg/ml / Brimonidina 2 mg/ml colirio en suspensión.
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	BRINZOLAMIDA
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	BRIMONIDINA TARTRATO
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 10 mg/ml colirio en suspensión
D.2.1.1.2	Name of the Marketing Authorisation holder	ALCON LABORATORIES LTD. (UK)
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	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	BRINZOLAMIDA
D.3.9.1	CAS number	138890-62-7
D.3.9.3	Other descriptive name	BRINZOLAMIDE
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	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	Brimonidina Tartrato 2 mg/ml Colirio en solución
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	BRIMONIDINA TARTRATO
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

Glaucoma de angulo abierto o hipertensión ocular/ Open-angle glaucoma or ocular hypertension

E.1.1.1

Medical condition in easily understood language

Presion elevada en el ojo (hipertensión ocular) o daños en el nervio óptico (glaucoma) / Elevated pressure in the eye with (ocular hypertension) or without optic nerve damages (glaucoma)

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	14.0
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Brinzolamida de 10 mg/ml / brimonidina 2 mg/ml, colirio en suspensión es superior a brinzolamida de 10 mg/ml, colirio en suspensión, con respecto a la eficacia para la reducción de la PIO; y brinzolamida 10 mg/ml / brimonidina 2 mg/ml, colirio en suspensión es superior a brimonidina 2 mg/ml, colirio en solución, con respecto a la eficacia para la reducción de la PIO -
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

No hay objetivos secundarios. There are no secondary objectives.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Pacientes de 18 años de edad o más, de ambos sexos y cualquier raza/etnicidad, diagnosticados de glaucoma de ángulo abierto o hipertensión ocular que, a criterio del investigador, carecen de control suficiente en la monoterapia o ya reciben medicación múltiple para reducir la PIO.
2. Los pacientes deben estar en condiciones de entender y firmar un consentimiento informado, aprobado por un Comité Ético.
3. Las medidas de PIO media en 1 ojo, en almenos un ojo el mismo ojo (o los mismos ojos), deben ser:
> o = 24 mmHg y < o = 36 mmHg en el punto de tiempo de las 9 de la mañana
> o = 21 mmHg y < o = 36 mmHg en el punto de tiempo de las 11 de la mañana en las Visitas de elegibilidad 1 y elegibilidad 2.
La PIO media no debe ser > 36 mmHg en ningún punto
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:
> o = 24 mmHg and < o = 36 mmHg at the 9 AM time point and,
> o = 21 mmHg and < o = 36 mmHg at the 11 AM time point at both E1 and E2 Visits.

E.4

Principal exclusion criteria

1 Mujeres en edad fértil (las que no han sido esterilizadas quirúrgicamente o posmenopáusicas durante 1 año como mínimo) se excluyen de la participación en el estudio si cumplen cualquier condición de las siguientes
a.están embarazadas o,
b. dan resultado positivo en la prueba de embarazo de orina en la visita de selección o,
c. tienen la intención de quedarse embarazadas durante el período del estudio o,
d. están en período de lactancia o,
e. no están usando medidas anticonceptivas de alta efectividad, como:
contraceptivos hormonales:
orales, implantados, transdérmicos o inyectados;
contraceptivos mecánicos:
espermicida junto con una barrera como un condón, diafragma o DIU.
2. Los pacientes con grado de ángulo de Schaffer < 2, medido por gonioscopia (ángulo extremadamente angosto con oclusión total o parcial).
3. Pacientes con relación copa/disco (C/D) superior a 0,80 (medida horizontal o vertical).
4. Pacientes con pérdida severa del campo visual central. La pérdida severa del campo visual central se define como una sensibilidad menor o igual a 10 dB en al menos 2 de los 4 puntos de prueba del campo visual más cercanos al punto de fijación.
5. Pacientes que no pueden interrumpir de forma segura el uso de toda la medicación ocular para reducir la PIO durante un período mínimo de 5 días ± 1 día hasta 28 días ± 1 día antes de la visita E1.
6. Retinopatía inflamatoria crónica, recurrente o severa (o sea, escleritis, uveitis, queratitis herpética).
7. Trauma ocular en los últimos 6 meses.
8. Infección ocular o inflamación ocular en los últimos 3 meses.
9. Retinopatía clínicamente significativa o progresiva, como degeneración retinal, retinopatía diabética o desprendimiento de la retina.
10. Un resultado de agudeza visual mejor corregida (BCVA) de menos de 55 letras ETDRS (equivalente a aproximadamente 20/80 Snellen, 0,60 logMAR, o 0,25 decimal).
11. Otras patologías oculares (entre ellas ojo seco severo) que, a criterio del investigador, son susceptibles de impedir la administración de agonista alfa-andrenérgico y/o inhibidor de anhidrasa carbónica tópica (CAI).
12. Cirugía intraocular en los últimos 6 meses.
13. Cirugía ocular láser en los últimos 3 meses
14. Cualquier anomalía que impida una tonometría de aplanación fiable
15. Cualquier otro estado, incluso enfermedades que, a criterio del investigador, harían que el paciente no fuera adecuado para el estudio.
16. Historial de enfermedad cardiovascular (insuficiencia coronaria, hipertensión, fenómeno de Raynaud, hipotensión ortostática, tromboanginitis obliterante, cerebrovascular (insuficiencia cerebral), hepática o renal, de carácter activo, severo, inestable o no controlada que, a criterio del investigador, impediría la administración segura de un agonista alfa-adrenérgico tópico o de un inhibidor de anhidrasa carbónica.
17. Pacientes con uso reciente (en las 4 semanas que preceden la visita de elegibilidad 1) de terapia de salicilato en dosis altas (> 1 g diario).
18. Tratamiento actual o previsto con cualquier fármaco psicotrópico que aumente la respuesta adrenérgica (desipramina, amitriptilina).
19. Uso simultaneo de inhibidores de monoamino oxidasa.
20. Terapia con otro agente de investigación dentro de los 30 días anteriores a la visita de selección.
21. Hipersensibilidad a los fármacos agonistas alfa-adrenérgicos, inhibidores de anhidrasa carbónica tópicos u orales, derivados de sulfonamida o a cualquier componente de la medicación del estudio, a criterio del investigador.
22. Menos de 30 días de régimen de dosificación estable antes de la visita de selección, de medicación o sustancias administradas por cualquier vía y usadas de forma crónica, que pueda afectar la PIO incluyendo pero sin limitación, agentes bloqueadores β-adrenérgicos.
23. Uso de una medicación hipotensiva ocular tópica o sistémica adicional durante el estudio.
24. Uso simultaneo de glucocorticoides administrados por cualquier vía.
El monitor médico puede declarar no adecuado a cualquier paciente por un motivo médico válido.

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.
2. 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

E.5 End points

E.5.1

Primary end point(s)

Eficacia Primaria:
Cambio de la PIO diurna media desde el valor inicial (mes 3).
Eficacia de apoyo:
Cambio de la PIO diurna media desde el valor inicial (semana 2, semana 6 y mes 6)
PIO media (semana 2, semana 6, mes 3 y mes 6)
Cambio de la PIO media desde el valor inicial (semana 2, semana 6, mes 3 y mes 6)
Cambio porcentual de la PIO media desde el valor inicial (semana 2, semana 6, mes 3 y mes 6)
Porcentaje de pacientes con PIO < 18 mmHg en cada visita en terapia y punto de tiempo (semana 2, semana 6, mes 3 y mes 6).
Seguridad: Paquimetría, parámetros de fondo del ojo, BCVA (agudeza visual mejor corregida), examen de lámpara de hendidura, perimetría automatizada estándar, pulso / presión sanguínea, acontecimientos adversos.
Primary Efficacy:
Mean diurnal IOP change from baseline (Month 3).
Supportive Efficacy:
Diurnal IOP change from baseline (Week 2, Week 6, Month 6)
IOP (Week 2, Week 6, Month 3, Month 6)
IOP change from baseline (Week 2, Week 6, Month 3, Month 6)
IOP % change from baseline (Week 2, Week 6, Month 3, Month 6)
Percentage of patients with IOP < 18 mmHg at each ontherapy visit and time point (Week 2, Week 6, Month 3, Month 6).)
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)

No procede

E.5.2.1

Timepoint(s) of evaluation of this end point

No procede

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.8.4.1

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

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

Última visita del último sujeto.

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