Clinical Trials Register

Summary
EudraCT Number:	2012-002938-37
Sponsor's Protocol Code Number:	AC2012-01
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-08-07
Trial 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

2012-002938-37

A.3

Full title of the trial

COMPARACIÓN DE LA EFICACIA Y DURACIÓN DEL EFECTO CLÍNICO DE ONABOTULINUMTOXINA A, INCOBOTULINUMTOXINA A Y ABOBOTULINUMTOXINA A PARA EL TRATAMIENTO DE LAS LÍNEAS GLABELARES DE MODERADAS A PROFUNDAS.

A.3.1

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

Comprobación del efecto clínico de tres toxinas botulínicas tipo A, sobre líneas verticales del entrecejo (líneas glabelares).

A.4.1

Sponsor's protocol code number

AC2012-01

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	DR. JAVIER ANIDO RUBIO
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merz Pharma S.A
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Clinica Gaztambide
B.5.2	Functional name of contact point	Dr. Javier Anido
B.5.3	Address:
B.5.3.1	Street Address	Rodríguez San Pedro, 66
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28015
B.5.3.4	Country	Senegal
B.5.4	Telephone number	91 544 24 93
B.5.5	Fax number	NA
B.5.6	E-mail	dr.anido@hotmail.com

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	Vistabel®
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Pharmaceuticals Ireland
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.3.1	Product name	Vistabel
D.3.2	Product code	Vistabel
D.3.4	Pharmaceutical form	Powder and solution for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Onabotulinumtoxina A (Vistabel®)
D.3.9.2	Current sponsor code	Onabotulinumtoxina A (Vistabel®)
D.3.10	Strength
D.3.10.1	Concentration unit	µl microlitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
D.2.1.1.1	Trade name	Bocouture®
D.2.1.1.2	Name of the Marketing Authorisation holder	Merz Pharma España S.L.
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.3.1	Product name	Bocouture
D.3.2	Product code	Bocouture
D.3.4	Pharmaceutical form	Powder and solution for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	incobotulinumtoxina A (Bocouture®)
D.3.9.2	Current sponsor code	incobotulinumtoxina A (Bocouture®)
D.3.10	Strength
D.3.10.1	Concentration unit	µl microlitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
D.2.1.1.1	Trade name	Azzalure®
D.2.1.1.2	Name of the Marketing Authorisation holder	Ipsen Pharma, S.A.
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.3.1	Product name	Azzalure
D.3.2	Product code	Azzalure
D.3.4	Pharmaceutical form	Powder and solution for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	? Abobotulinumtoxina A (Azzalure®)
D.3.9.2	Current sponsor code	? Abobotulinumtoxina A (Azzalure®)
D.3.10	Strength
D.3.10.1	Concentration unit	µl microlitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

Se trata de sujetos que requieren tratamiento con toxina botulínica para las arrugas del entrecejo (líneas glabelares) de moderadas a profundas.

E.1.1.1

Medical condition in easily understood language

Sujetos con arrugas en el entrecejo a los cuales se les tratará con toxinas botulínicas tipo A

E.1.1.2

Therapeutic area

Not possible to specify

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

El objetivo de este estudio es comprobar y comparar la eficacia de incobotulinumtoxina A, onabotulinumtoxina A y abobotulinuntoxina A, pasadas 4 y 16 semanas desde su administración, en el tratamiento de las líneas glabelares en máximo fruncimiento (dinámicas) y en reposo, cuando se utilizan a dosis equipotentes de las tres toxinas (ratio 1:1:2,5, respectivamente) (Roggenkämper, 2006; Benecke, 2005), valorando también de esta forma la duración de los tratamientos. La evaluación se realiza por el investigador según las escalas Merz Aesthetics Scales

E.2.2

Secondary objectives of the trial

Evaluar la tolerancia y seguridad mediante la valoración de la incidencia de efectos adversos emergentes tras la administración de cualquiera de las toxinas botulínicas tipo A:
-local en la zona de administración
-general, mediante la valoración de los acontecimientos adversos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Solamente se considerarán para su inclusion en el ensayo clínico los sujetos que cumplan todos los criterios de inclusion siguientes:
?Mujeres (50%) y varones (50%) entre 35-50 años
?Líneas verticales entre las cejas (líneas glabelares) de intensidad moderada a grave en máximo fruncimiento (puntuación de intensidad de 2 a 3 en la escala de arrugas faciales de Merz (Merz Aesthetics Scales).
?Sin tratamiento previo (50%) o tratamiento previo satisfactorio (50%) de las lineas glabelares con cualquiera de las toxinas botulínicas tipo A utilizadas en el presente ensayo clínico.
?Consentimiento informado por escrito de los sujetos.

E.4

Principal exclusion criteria

Los sujetos no deberán presentar ninguno de los criterios de exclusión siguientes para poder participar en el estudio:
?Líneas / arrugas muy profundas (grado 4 en la Merz Aesthetics Scales)
?Embarazo o lactancia
?Exacerbaciones de enfermedades crónicas
?Intolerancia a la Toxina Botulínica tipo A
?Tratamiento previo con rellenos biodegradables o ácido hialurónico en el rostro, durante los últimos 12 meses.
?Cualquier cirugía en la zona facial
?Cicatrices en la zona facial
?Cualquier otro procedimiento cosmético en el rostro planificado durante el presente estudio.
?Rejuvenecimiento facial con laser o mediante cualquier otra técnica en las últimas seis semanas
?Tendencia a formación de queloides o historia de granulomas
?Sujetos con vello facial excesivo que pueda interferir con la valoración de las arrugas.
?Marcada asimetría facial.
?Piel sebácea gruesa o músculos hipertróficos en el rostro.
?Antecedentes de parálisis facial.
?Antecedentes de shock anafiláctico (o reacción alérgica grave) en el pasado
?Reacción alérgica a lidocaina
?Tratamiento con cualquier especialidad farmacéutica con isotretinoina en los últimos 12 meses.
?Infección en la zona de inyección
?Tratamiento con antibióticos aminoglucósidos
?Cualquier enfermedad sistémica grave o no controlada (por ejemplo, cardiaca, renal, pulmonar, hepatica o gastrointestinal), epilepsia, diabetes, enfermedad autoimmune (por ejemplo, atritis reumatoide), depresión, tumor maligno, o antecedentes médicos de infección por VIH

E.5 End points

E.5.1

Primary end point(s)

La variable principal de eficacia es la proporción de pacientes con reducción en la puntuación de la escala Merz (al menos un punto) de valoración de las líneas glabelares en máximo fruncimiento entre el momento basal y después de 4 semanas de haber administrado el tratamiento. Para evaluar la significación estadística se calcularán los intervalos de confianza bilateral al 90% de la diferencia de proporciones 2 a 2 y se evaluará si el límite inferior de cada intervalo se aleja del cero en más de un 15%.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 SEMANAS

E.5.2

Secondary end point(s)

En cuanto a la eficacia, se repetirá el análisis completo especificado para las variables principales pero teniendo en cuenta la reducción en la puntuación de la escala entre el momento basal y después de 16 semanas de haber administrado el tratamiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

16 SEMANAS

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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

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)

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.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)

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

2012-09-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-07

P. End of Trial
P.	End of Trial Status	Ongoing

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