Clinical Trials Register

Summary
EudraCT Number:	2009-011135-13
Sponsor's Protocol Code Number:	BIA-2093-311
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:	2010-06-23
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

2009-011135-13

A.3

Full title of the trial

EFFICACY AND SAFETY OF ESLICARBAZEPINE ACETATE (BIA 2-093) AS MONOTHERAPY FOR PATIENTS WITH NEWLY DIAGNOSED PARTIAL-ONSET SEIZURES: A DOUBLE-BLIND, RANDOMIZED, ACTIVE-CONTROLLED, PARALLEL-GROUP, MULTICENTER CLINICAL STUDY

EFICACIA Y SEGURIDAD DEL ACETATO DE ESLICARBAZEPINA (BIA 2-093) COMO MONOTERAPIA PARA PACIENTES CON NUEVO DIAGNÓSTICO DE CRISIS DE COMIENZO PARCIAL: ESTUDIO DOBLE CIEGO, ALEATORIZADO, COMPARADO CON FÁRMACO ACTIVO, DE GRUPOS PARALELOS Y MULTICÉNTRICO

A.4.1

Sponsor's protocol code number

BIA-2093-311

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	BIAL - Portela & Ca, S.A.
B.1.3.4	Country	Portugal
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	Eslicarbazepine Acetate
D.3.2	Product code	BIA 2-093
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Eslicarbazepine Acetate
D.3.9.1	CAS number	236395-14-5
D.3.9.2	Current sponsor code	BIA 2-093
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Eslicarbazepine Acetate
D.3.9.1	CAS number	236395-14-5
D.3.9.2	Current sponsor code	BIA 2-093
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	800
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	Tegretal retard
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Carbamazepine controlled-release
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carbamazepine controlled-release
D.3.9.1	CAS number	298-46-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carbamazepine controlled-release
D.3.9.1	CAS number	298-46-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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	Tegretol XR
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharmaceuticals Corporation, NJ
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Carbamazepine controlled-release
D.3.4	Pharmaceutical form	Over encapsulated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carbamazepine controlled-release
D.3.9.1	CAS number	298-46-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Capsule*
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule*
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule*
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adult patients with newly diagnosed partial-onset seizures

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	10065336
E.1.2	Term	Partial epilepsy

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate that monotherapy with Eslicarbazepine Acetate (ESL; 800 to 1600 mg once daily) is not inferior to monotherapy with controlled-release carbamazepine (CBZ-CR; 200 to 600 mg twice daily) in adults (?18 years) with newly diagnosed epilepsy experiencing partial-onset seizures.

E.2.2

Secondary objectives of the trial

To further demonstrate the efficacy, safety, and pharmacokinetics of ESL in this patient population at the doses used.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Visita 1 (Días –1 a –7)

1. Haber firmado un consentimiento informado antes de que comience cualquier la actividad relacionada con el estudio. Los sujetos descendientes de asiáticos deberán dar su consentimiento informado escrito para la realización de genotipado.
2. Ser varón o mujer ≥18 años de edad.
3. Presentar epilepsia recién diagnosticada con al menos 2 crisis parciales bien documentadas, clínicamente evaluadas y no provocadas (con o sin generalización secundaria) con un origen focal claro, documentadas clínicamente mediante electroencefalograma (EEG) o pruebas de imagen en los 12 meses anteriores a la visita 1.
4. Haber presentado al menos 1 crisis durante los 3 meses anteriores.
5. Cooperación y disposición demostradas para completar todos los aspectos del estudio.
6. Las pacientes que no están en edad fértil (2 años en posmenopausia, haber sufrido una ooforectomía bilateral o ligadura de trompas o una histerectomía completa) son aptas para participar en el estudio. Las pacientes que están en edad fértil no pueden estar embarazadas, confirmado mediante una prueba negativa de ß-gonadotropina coriónica humana (hCG) en suero, y las pacientes sexualmente activas deben utilizar un método anticonceptivo no hormonal, de doble barrera, eficaz y médicamente aceptable durante todo el estudio y hasta finalizar la visita posterior al estudio (PSV).
Visita A1, Día 1 (visita de aleatorización e inicio del periodo de tratamiento doble ciego)
7. Haber completado de forma satisfactoria el diario electrónico del sujeto (diario-e)
8. Las pacientes que están en edad fértil no pueden estar embarazadas, confirmado mediante una prueba negativa de embarazo en orina, y las pacientes sexualmente activas deben utilizar un método anticonceptivo no hormonal, de doble barrera, eficaz y médicamente aceptable durante todo el estudio y hasta finalizar PSV.

E.4

Principal exclusion criteria

Visita 1 (Días –1 a –7)

1. Antecedentes de pseudocrisis
2. Crisis que sólo se producen en acúmulos.
3. Sujetos con antecedentes de crisis de ausencia, mioclónicas, clónicas, tónicas o atónicas
4. EEG documentado en los 12 meses anteriores a la visita 1 que sugiera epilepsia principalmente generalizada.
5. Antecedentes de status epilepticus en los 3 meses anteriores a la Visita 1.
6. Trastorno neurológico progresivo conocido (enfermedad cerebral progresiva, epilepsia secundaria a una lesión cerebral progresiva), evaluado mediante resonancia magnética o tomografía computerizada.
7. Antecedentes de esquizofrenia o intento de suicidio.
8. Uso pasado o presente de cualquier FAE, a excepción del uso de un único FAE durante un máximo de 2 semanas antes de la Visita 1.
9. Uso previo de ESL o CBZ.
10. Estar utilizando inhibidores de la monoaminoxidasa (IMAO), antidepresivos tricíclicos, nefazodona o isoniazida.
11. Hipersensibilidad conocida a los derivados de carboxamida o a los antidepresivos tricíclicos.
12. Antecedentes de alcoholismo, drogadicción o abuso de medicamentos en los últimos 2 años.
13. Trastorno cardíaco (incluido el bloqueo auriculoventricular y otras anomalías electrocardiográficas clínicamente significativas), renal, hepático, endocrino, gastrointestinal, metabólico, hematológico u oncológico no controlado.
14.Antecedentes de depresión de médula ósea.
15.Antecedentes de porfirias hepáticas (p. ej., porfiria intermitente aguda, porfiria variegata, porfiria cutánea tardía).
16.Anomalías analíticas clínicas relevantes (p. ej., niveles de sodio <130 mmol/l, niveles de alanina o aspartato transaminasas >2 x el límite superior de la normalidad, recuento de glóbulos blancos <3000 células/mm3) (medidos en la Visita 1).
17.Tasa de filtración glomerular estimada (TFGe) <60 ml/min/1,73 m2 (medida en la Visita 1).
18. Los sujetos descendientes de asiáticos con una prueba positiva para la presencia del alelo HLA-B*1502.
19. Embarazo o lactancia.
20. Participación en otro ensayo clínico con fármacos en los últimos 2 meses o haber recibido un PEI dentro de 5 semividas de dicho PEI, lo que sea más prolongado.
21. Cualquier otra afección o circunstancia que, en opinión del investigador, pueda comprometer la capacidad por parte del paciente de seguir el protocolo del estudio.

Visita A1, Día 1 (visita de aleatorización e inicio del periodo de tratamiento doble ciego)

22. Uso pasado o presente de cualquier FAE, a excepción del uso de un único FAE durante un máximo de 2 semanas antes de la Visita 1 y con un periodo sin fármacos de al menos 5 días previos a la Visita A1. Se permite el uso de benzodiacepinas, no más de dos veces a la semana, para una indicación de epilepsia y como medicación de rescate durante el periodo de ≥ 5 días sin fármacos.
23. Estar utilizando IMAO, antidepresivos tricíclicos, nefazodona o isoniazida.
24. Embarazo.
25. Cualquier otra afección o circunstancia que, en opinión del investigador, pueda comprometer la capacidad por parte del paciente de seguir el protocolo del estudio.

E.5 End points

E.5.1

Primary end point(s)

Proporción de sujetos em la poblacion por protocolo que permanecen sin crisis durante el periodo de Evaluación de 26 semanas al último nivel de dosis asignado.

Proportion of subjects in the per protocol set who are seizure free for the entire 26-week Evaluation Period at the last received dose level.

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

Yes

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

102

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

Information not present in EudraCT

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

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

The end of the study is triggered by the date of the last visit for the last subject who completes the 26-week Evaluation Period.
When the timing is known for the last subject to attend their End-of-Evaluation Period visit (Visit A4, B4, or C4), all centers will be instructed to contact all subjects and schedule this last Extension Phase Visit.

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2010-06-23.

Yes

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

479

F.4.2.2

In the whole clinical trial

900

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)

At the last Extension Phase Visit investigators will determine if it is in subject's best interest to continue in a further Extension Phase, which will be described in a separate protocol, or to discontinue with the investigational product.
In case of discontinuation, subjects will be treated according to local standard practice.

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

2010-08-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-07-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-08

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