Clinical Trials Register

Summary
EudraCT Number:	2010-022984-36
Sponsor's Protocol Code Number:	201051
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:	2010-12-23
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

Spain - AEMPS

A.2

EudraCT number

2010-022984-36

A.3

Full title of the trial

Estudio clínico en fase III, aleatorizado y doble ciego de 6 meses de duración para comparar la eficacia y la seguridad del colirio de combinación de dosis fijas de tafluprost al 0,0015% y timolol al 0,5% sin conservantes con las de los colirios de tafluprost al 0,0015% y timolol al 0,5% administrados simultáneamente en pacientes con glaucoma de ángulo abierto o hipertensión ocular.

A phase III, randomized, double-masked 6-month clinical study to compare the efficacy and safety of the preservative-free fixed dose combination of tafluprost 0.0015% and timolol 0.5% eye drops to those of tafluprost 0.0015% and timolol 0.5% eye drops given concomitantly in patients with open angle glaucoma or ocular hypertension.

A.3.2

Name or abbreviated title of the trial where available

Estudio de no inferioridad de combinación de dosis fija de tafluprost-timolol comparado con administ

A.4.1

Sponsor's protocol code number

201051

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Santen Oy
B.1.3.4	Country	Finland
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	Combinación de una dosis fija sin conservantes de tafluprost al 0,0015% y de timolol al 0,5%
D.3.2	Product code	FDC
D.3.4	Pharmaceutical form	Eye drops, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	DE-111A
D.3.9.3	Other descriptive name	TAFLUPROST
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.0015
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	DE-111A
D.3.9.3	Other descriptive name	TIMOLOL
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Taflotan Nota: forma farmacéutica de dosis única sin conservantes.
D.2.1.1.2	Name of the Marketing Authorisation holder	Santen Oy
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	209860-87-7
D.3.9.3	Other descriptive name	Tafluprost
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.0015
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.2.1.1.1	Trade name	Oftan Timolol Nota: forma farmacéutica de dosis única sin conservantes.
D.2.1.1.2	Name of the Marketing Authorisation holder	Santen Oy
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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, solution
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	TIMOLOL MALEATO
D.3.9.1	CAS number	26921-17-5
D.3.9.3	Other descriptive name	Oftan Timolol
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Eye drops, solution
D.8.4	Route of administration of the placebo	Ocular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pacientes con diagnóstico de hipertensión ocular o glaucoma de ángulo abierto (glaucoma primario de ángulo abierto, glaucoma capsular o glaucoma pigmentario).

Patients diagnosed with ocular hypertension or open-angle glaucoma (primary open-angle glaucoma [POAG], capsular glaucoma or pigmentary glaucoma).

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10030043
E.1.2	Term	Ocular hypertension

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10036719
E.1.2	Term	Primary open angle glaucoma

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10035015
E.1.2	Term	Pigmentary glaucoma

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10037118
E.1.2	Term	Pseudoexfoliation glaucoma

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

El objetivo de este estudio es comparar la eficacia y la seguridad del colirio de combinación de dosis fijas de tafluprost al 0,0015% y timolol al 0,5% sin conservante con las de los colirios de tafluprost al 0,0015% y de timolol al 0,5% sin conservantes administrados simultáneamente.

Variable principal de eficacia:
o Variación respecto al valor basal de la PIO diurna media a los 6 meses

El objetivo principal de este studio es demostrar que después de un periodo de tratamiento de 6 meses la combinación de dosis fija sin conservantes administrada una vez al día no es inferior a la administración concomitante de tafluprost al 0,0015% una vez al día y timolol al 0.5% dos veces al día en pacientes con glaucoma de ángulo abierto o hipertensión ocular.

E.2.2

Secondary objectives of the trial

Variables secundarias de eficacia:
o Proporción de pacientes con respuesta (por ejemplo, una reducción de la PIO del 20% o una PIO de 16 mm Hg o menos) a los 6 meses
o Variación respecto al valor basal de la PIO diurna media a las 2 semanas, 6 semanas y 3 meses
o Variación respecto al valor basal de la PIO en cada momento de administración (a las 8:00, 10:00 y 16:00) a las 2 semanas, 6 semanas, 3 meses y 6 meses

Evaluación de la seguridad y la tolerabilidad de la combinación de dosis fija frente a la administración concomitante de tafluprost y timolol:
o Acontecimientos adversos
o Agudeza visual
o Espesor central de la córnea
o Enrojecimiento conjuntival
o Biomicroscopia
o Oftalmoscopia
o Exploración del campo visual
o Presión arterial y frecuencia cardíaca en reposo
o Molestias generales causadas por los colirios

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Podrá incluirse en el estudio a los pacientes de cualquier raza y de los dos sexos que cumplan todos los criterios siguientes:
1. Dieciocho años de edad o más
2. Diagnóstico de hipertensión ocular o glaucoma de ángulo abierto (GAAP, glaucoma capsular o glaucoma pigmentario) en uno o ambos ojos
3. Necesidad clínica de añadir un fármaco reductor de la PIO según el criterio del investigador y una PIO no tratada (tras un período de lavado, si procede) > ó = 23 mm Hg en la determinación basal a las 8:00 horas en uno o ambos ojos
4. Los pacientes que hayan recibido medicación previa para el glaucoma deben tener el siguiente período de lavado mínimo:
> ó = 4 semanas en caso de administración de antagonistas adrenérgicos Beta (betabloqueantes)
> ó = 4 semanas en caso de prostamidas o análogos de las prostaglandinas
> ó = 3 semanas en caso de agonistas alfa-adrenérgicos (alfa-agonistas)
> ó = 7 días en caso de inhibidores de la anhidrasa carbónica (IAC)
> ó = 5 días en caso de mióticos
5. Una mejor puntuación de agudeza visual con corrección determinada con el método ETDRS de +0,6 logAMR o superior en ambos ojos (es decir, no cumplen los criterios los pacientes con afectación monocular)
6. Disponibilidad a seguir las instrucciones
7. Consentimiento informado por escrito.

E.4

Principal exclusion criteria

1. Mujeres embarazadas, lactantes o que planeen quedarse embarazadas, o mujeres en edad fértil que no utilicen un método fiable de anticoncepción
2. Ángulo de la cámara anterior en uno de los ojos a tratar menor de grado 2 según la clasificación Schaffer, medido por gonioscopia
3. Cualquier anomalía corneal u otro trastorno que impida la tonometría de aplanación fiable en los ojos tratados, incluida la cirugía previa de la refracción ocular
4. PIO mayor de 36 mm Hg en cualquier momento en cualquier ojo en las visitas de selección o basal
5. Diagnóstico de glaucoma de ángulo cerrado o glaucoma secundario diferente del glaucoma capsular o pigmentario en cualquier ojo
6. Sospecha de contraindicación a tafluprost o timolol:
o hipersensibilidad a tafluprost/timolol o a cualquiera de los excipientes
o frecuencia cardíaca baja <50 lpm (en la visita de selección) o presión arterial baja clínicamente relevantes para la edad, enfermedad pulmonar obstructiva crónica, asma bronquial, marcada tendencia a broncoespasmo, determinadas arritmias cardíacas, las más frecuentes de las cuales son el bloqueo AV de segundo o tercer grado y la bradicardia, o insuficiencia cardiaca congestiva no controlada
o además, para el lavado del medicamento Azopt® (cuyo uso debe valorar el investigador): hipersensibilidad a brinzolamida o a cualquiera de los excipientes, hipersensibilidad conocida a sulfamidas, insuficiencia renal grave o acidosis hiperclorémica
7. Cirugía de filtración del glaucoma u otra cirugía ocular (incluidos los procedimientos oculares con láser) en los 6 meses previos a la selección en uno o ambos ojos que vayan a recibir tratamiento con la medicación del estudio
8. Uso de lentes de contacto en la selección o durante el estudio
9. Defecto del campo visual avanzado en cualquier ojo o progresión prevista durante el estudio a criterio del investigador
10. Imposibilidad de interrumpir sin peligro el uso de hipotensores oculares durante el período de lavado
11. Cualquier enfermedad o trastorno oculares (por ejemplo, afaquia, pseudoafaquia con desgarro de la cápsula posterior del cristalino o de la cámara anterior del cristalino, factores de riesgo conocidos de edema macular quística o iritis/uveítis), sistémicos o psiquiátricos (por ejemplo, hipertensión arterial no controlada, diabetes) que puedan poner suponer un peligro importante para el paciente o confundir los resultados del estudio, o interferir de forma significativa en su participación en el estudio a criterio del investigador
12. Cambio de un tratamiento crónico previo que pudiera afectar significativamente a la PIO o a los resultados del estudio en los 30 días previos a la visita 1, o cambios esperados en estos tratamientos durante el estudio
13. Alcoholismo o toxicomanía en el momento actual
14. Participación actual en otro ensayo clínico con un fármaco o producto sanitario en investigación, o participación en un estudio en los 30 días anteriores.

E.5 End points

E.5.1

Primary end point(s)

Variación respecto al valor basal de la PIO diurna media a los 6 meses.

Las valoraciones diurnas de la PIO se realizará a las 8:00 (+/- 1 h), 10:00 (+/- 1 h) y a las 16:00 (+/- 1 h).

La evaluación primaria de la PIO se basará en el ojo que esté peor.

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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.8.3

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

Information not present in EudraCT

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

Como se detalla en el protocolo.

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

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

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

380

F.4.2.2

In the whole clinical trial

380

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)

Como se define en el protocolo

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

2011-02-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-05-03

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