Clinical Trials Register

Summary
EudraCT Number:	2015-001243-36
Sponsor's Protocol Code Number:	BIA-2093-311/EXT
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-02-09
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-001243-36

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 - Open-label ESL extension -

Efficacia e sicurezza di eslicarbazepina acetato (BIA 2-093) come monoterapia per pazienti con crisi epilettiche parziali di nuova diagnosi: studio clinico in doppio cieco, randomizzato, con farmaco di controllo, a gruppi paralleli, multicentrico
- Estensione ESL in aperto -

A.3.1

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

Efficacy and safety of eslicarbazepine acetate (BIA 2-093) as monotherapy for patients with newly diagnosed partial-onset seizures - open label extension study with eslicarbazepine acetate

Efficacia e sicurezza di eslicarbazepina acetato (BIA 2-093) come monoterapia per pazienti con crisi epilettiche parziali di nuova diagnosi - studio di estensione in aperto con eslicarbazepina acetato

A.3.2

Name or abbreviated title of the trial where available

not applicable

non applicabile

A.4.1

Sponsor's protocol code number

BIA-2093-311/EXT

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02484001

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	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	European Investment Bank
B.4.2	Country	Luxembourg
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BIAL - Portela & Ca, S.A.
B.5.2	Functional name of contact point	Sponsor
B.5.3	Address:
B.5.3.1	Street Address	¿ Av. Siderurgia Nacional
B.5.3.2	Town/ city	Coronado (S. Rom¿o e S. Mamede)
B.5.3.3	Post code	4745-457
B.5.3.4	Country	Portugal
B.5.4	Telephone number	00351229866100
B.5.5	Fax number	00351229866192
B.5.6	E-mail	jose.rocha@bial.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	Eslicarbazepina Acetato
D.3.2	Product code	BIA 2-093
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
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	ESLICARBAZEPINA ACETATO
D.3.9.1	CAS number	236395-14-5
D.3.9.2	Current sponsor code	BIA 2-093
D.3.9.3	Other descriptive name	Eslicarbazepine acetate
D.3.9.4	EV Substance Code	SUB30424
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)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
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	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

Adult patients with recently diagnosed partial-onset seizures

Pazienti adulti con nuova diagnosi di crisi parziali epilettiche

E.1.1.1

Medical condition in easily understood language

Adult patients with recently diagnosed partial epilepsy

Pazienti adulti con nuova diagnosi di epilessia parziale

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10065336
E.1.2	Term	Partial epilepsy
E.1.2	System Organ Class	100000004852

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 confirm maintenance of efficacy of eslicarbazepine acetate (ESL, 800 mg to 1600 mg once daily [QD]) monotherapy during long-term treatment in adults (=18 years) with recently diagnosed epilepsy experiencing partial-onset seizures.

Confermare il mantenimento dell'efficacia di eslicarbazepina acetato (ESL, da 800 mg a 1600 mg una volta al giorno) in monoterapia durante il trattamento a lungo termine in adulti (=18 anni) con epilessia di recente diagnosi che manifestano crisi a esordio parziale.

E.2.2

Secondary objectives of the trial

1. To further demonstrate the efficacy of ESL in subjects switching from carbamazepine controlled-release (CBZ-CR) treatment.
2. To demonstrate the safety of ESL in subjects switching from CBZ-CR treatment and in subjects already treated with ESL monotherapy for at least one year (i.e. during long-term treatment).

1. Dimostrare ulteriormente l'efficacia di ESL in soggetti che hanno effettuato il passaggio dal trattamento con carbamazepina a rilascio controllato (CBZ-CR).
2. Dimostrare la sicurezza di ESL nei soggetti che hanno effettuato il passaggio dal trattamento con CBZ-CR e nei soggetti gi¿ trattati con ESL in monoterapia da almeno un anno (cio¿ durante il trattamento a lungo termine).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For inclusion in the extension study, subjects must fulfill all of the following at Visit 1 (Day 1, start of the open-label extension study):
1. Participated in the preceding double-blind study and were still ongoing at the time of unblinding.
2. Have signed informed consent before undergoing any activities related to the open-label extension study.
3. Demonstrated cooperation and willingness to complete all aspects of the study.
4. Female subjects without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative serum ß-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the Post-study Visit (PSV).

Per l'inclusione nello studio di estensione, i soggetti devono soddisfare tutti i requisiti seguenti alla Visita 1 (Giorno 1, inizio dello studio di estensione in aperto):
1. Aver partecipato al precedente studio in doppio cieco e ancora partecipanti al momento dello svelamento del cieco.
2. Avere firmato il consenso informato prima di sottoporsi a qualunque attività correlata allo studio di estensione in aperto.
3. Aver dimostrato spirito collaborativo e intenzione di completare tutti gli aspetti dello studio.
4. I soggetti di sesso femminile non potenzialmente fertili (2 anni post-menopausa, ovariectomia bilaterale o legatura delle tube o isterectomia completa) sono idonei. I soggetti di sesso femminile potenzialmente fertili non devono essere incinte come confermato da un test sierico negativo della beta gonadotropina corionica umana (hCG) e le donne sessualmente attive devono utilizzare un metodo di contraccezione efficace, non ormonale, clinicamente accettabile per la durata dello studio e fino alla visita post-studio (Post-study Visit, PSV).

E.4

Principal exclusion criteria

Subjects having any of the following at Visit 1 are to be excluded from the study:
1. Excluded from the double-blind study due to seizure in the Maintenance or Extension Phase, or at dose level C (either CBZ-CR or ESL), or discontinued prematurely due to any other reason in the double blind study.
2. Presence of any major protocol violation during the double-blind study which may have an impact on the compliance during this extension study.
3. Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide- Severity Rating Scale (C-SSRS).
4. Occurrence of an adverse event (AE) indicating a suspected presence of atrioventricular block (2nd degree and above) or of any other AEs during the double-blind study which are judged by the investigator as contraindicative to further participation in the open-label extension study.
5. Events of alcohol, drug, or medication abuse during the preceding double-blind study.
6. Relevant clinical laboratory abnormalities (e.g. sodium <125 mmol/L, alanine or aspartate transaminases >2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (as reported at Visit 1).
7. Pregnancy or lactating.
8. Any oth r condition or circumstance that, in the opinion of the investigator, could compromise the subject's ability to comply with the extension-study protocol.

I soggetti che presentano uno qualsiasi dei fattori seguenti alla Visita 1 devono essere esclusi dallo studio:
1. Esclusi dallo studio in doppio cieco a causa di crisi durante la Fase di mantenimento o di estensione, o al livello di dose C (CBZ-CR o ESL), o sospesi prematuramente a causa di qualsiasi altro motivo nello studio in doppio cieco.
2. Presenza di qualsiasi violazione del protocollo importante durante lo studio in doppio cieco che possa influenzare la compliance durante il presente studio di estensione.
3. Giudicati clinicamente a rischio di suicidio nell'opinione dello sperimentatore in base a un colloquio clinico e alla Scala della Columbia University per la valutazione della gravità del rischio di suicidio (Columbia Suicide-Severity Rating Scale, C-SSRS).
4. Verificarsi di un evento avverso (adverse event, AE) che indica il sospetto di presenza di blocco atrioventricolare (di 2° grado e superiore) o di qualsiasi altro AE durante lo studio in doppio cieco che sia giudicato dallo sperimentatore come una controindicazione all'ulteriore partecipazione nello studio di estensione in aperto.
5. Episodi di abuso di alcol, droghe o farmaci durante il precedente studio in doppio cieco.
6. Valori di laboratorio clinici pertinenti anormali (ad esempio sodio <125 mmol/L, alanina o aspartato transaminasi >2 x il limite superiore della norma, conta leucocitaria <3000 cellule/mm3) (in base ai dati della Visita 1).
7. In gravidanza o in allattamento.
8. Qualsiasi altra condizione o circostanza che, nel parere dello sperimentatore, potrebbe compromettere la capacità del soggetto di rispettare il protocollo dello studio di estensione.

E.5 End points

E.5.1

Primary end point(s)

Time to treatment failure, defined as time from start of open-label ESL
treatment at Visit 1 until withdrawal due to AE or due to lack of efficacy
(i.e. inadequate seizure control).

• Tempo all'insuccesso, definito come il tempo dall'inizio trattamento in aperto con ESL alla Visita 1 fino alla sospensione a causa di AE o di mancanza di efficacia (cioè inadeguato controllo delle crisi).

E.5.1.1

Timepoint(s) of evaluation of this end point

at least 1 year

almeno 1 anno

E.5.2

Secondary end point(s)

¿ Treatment retention time (overall, i.e. including previously CBZ-CR
treated subjects, and by reason) at the last evaluated dose during openlabel
treatment, where treatment retention time is defined as the time
from start of the extension study until withdrawal of ESL due to AEs or
due to lack of efficacy (i.e. inadequate seizure control).
¿ Time to withdrawal for any reason at the last evaluated dose.
¿ Changes in quality of life assessed using the QOLIE-31.
¿ Changes in overall treatment satisfaction as assessed on a 4-point
scale.

¿ Tempo di mantenimento del trattamento (nel complesso, cio¿ compresi i soggetti trattati in precedenza con CBZ-CR, e in base al motivo) all'ultima dose valutata durante il trattamento in aperto, ove il tempo di mantenimento del trattamento viene definito come il tempo dall'inizio dello studio di estensione fino alla sospensione di ESL a causa di AE o di mancanza di efficacia (cio¿ inadeguato controllo delle crisi).
¿ Tempo alla sospensione per qualunque motivo all'ultima dose valutata.
¿ Variazioni nella qualit¿ della vita valutate utilizzando il QOLIE-31.
¿ Variazioni nella soddisfazione complessiva nei riguardi del trattamento valutate su una scala a 4 punti.

E.5.2.1

Timepoint(s) of evaluation of this end point

At least 1 year; Almeno 1 anno

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

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

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

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

Argentina

Australia

Brazil

Chile

Israel

Peru

Russian Federation

Serbia

Ukraine

Austria

Belgium

Bulgaria

Croatia

Estonia

Finland

France

Germany

Hungary

Italy

Latvia

Lithuania

Poland

Portugal

Romania

Slovakia

Spain

Sweden

United Kingdom

Czechia

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 complete study duration including treatment with ESL under open label conditions and follow-up is expected to last approximately 2 years
(105 weeks). In case ESL as monotherapy will achieve MA prior to the end of 2017, the study may be discontinued prematurely within 42 days after achievement of MA.

La durata totale dello studio che include il trattamento con ESL in aperto
e il follow-up dovrebbe essere di circa 2 anni
(105 settimane).
Nel caso in cui ESL come monoterapia raggiunger¿ l'AIC prima della fine del 2017, lo studio potrebbe essere interrotto prematuramente entro 42 giorni dopo il raggiungimento dell'AIC.

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

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:

279

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

175

F.4.2.2

In the whole clinical trial

300

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)

After the Trial subjects will be treated according to local standard medical practice.

Dopo lo studio i pazienti verranno trattati in accordo alla locale pratica clinica standard.

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

2015-12-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-19

P. End of Trial
P.	End of Trial Status	Completed

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