Clinical Trials Register

Summary
EudraCT Number:	2007-001887-55
Sponsor's Protocol Code Number:	SCO/BIA-2093-305
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2007-07-09
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

Portugal - INFARMED

A.2

EudraCT number

2007-001887-55

A.3

Full title of the trial

Efficacy and safety of eslicarbazepine acetate (BIA 2-093) as adjunctive therapy for refractory partial seizures in children: a double-blind, randomised, placebo-controlled, parallel-group, multicentre clinical trial

A.3.1

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

Eslicarbazepine Acetate (BIA 2-093) as Therapy for Refractory Partial Seizures in Children

A.4.1

Sponsor's protocol code number

SCO/BIA-2093-305

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00988156

A.7

Trial is part of a Paediatric Investigation Plan

Yes

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	BIAL - Portela & Ca, S.A.
B.4.2	Country	Portugal
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	Dep. of Research and Development
B.5.3	Address:
B.5.3.1	Street Address	À Av. Siderurgia Nacional
B.5.3.2	Town/ city	S. Mamede do Coronado
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	teresa.nunes@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	Eslicarbazepine acetate
D.3.2	Product code	BIA 2-093
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Yes
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	200
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	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	Oral suspension
D.3.4.1	Specific paediatric formulation	Yes
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/ml milligram(s)/millilitre
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
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	Oral suspension
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

children and adolescents with refractory partial epileptic seizures

E.1.1.1

Medical condition in easily understood language

Epilepsy / Partial onset seizures

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10015037
E.1.2	Term	Epilepsy
E.1.2	System Organ Class	10029205 - Nervous system 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

The primary objective of the study is to assess the efficacy of eslicarbazepine acetate as adjunctive therapy in children and adolescents with refractory partial seizures.
The primary analysis variables for the assessment of efficacy will be:
1. the responder rate, defined as the proportion of patients with at least a 50% decrease in the standardised seizure frequency
2. the relative reduction in the standardised seizure frequency

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are:
• To assess the safety and tolerability of eslicarbazepine acetate as adjunctive therapy in children and adolescents with refractory partial seizures
• To assess the proportion of seizure-free patients and of patients with more than 75% reduction in seizure frequency
• To assess the frequency of patients with exacerbations
• To assess the duration of seizures and severity of seizures (using the Hague seizure severity scale)
• To assess the potential for rebound effects and withdrawal phenomena
• To assess the potential for interactions between eslicarbazepine acetate and concomitant AED medication
• To assess the seizure frequency by seizure type
• To assess the maintenance of the therapeutic effect of eslicarbazepine acetate during long-term treatment in Part II of the study

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria
• Children aged 2 to 18 years
• Young girls of child bearing potential have to follow a reliable and medically acceptable contraceptive method during all duration of the study
• Diagnosis of epilepsy for at least 6 months prior to enrolment
• At least 4 partial-onset seizures in the last month prior to enrolment despite stable therapy with adequate dosage of 1 or 2 AEDs
• At least 4 partial-onset seizures during each 4 week interval of the 8 week baseline period
• Previous treatment with three or more AEDs, in their maximum tolerated doses, for at least one month, without seizure control
• Current treatment with 1 or 2 AEDs (any AED except oxcarbazepine); if present, vagus stimulation is considered an AED
• Stable dose regimen of AEDs during the 8 week baseline period
• Cooperation and willingness to complete all aspects of the study, including hospitalisation if required
• Written informed consent to participate in the study in accordance with local legislation

E.4

Principal exclusion criteria

• Primarily generalised seizures
• Baseline seizure frequency aubstantially different from usual aeizure frequency
• Known progressive neurological disorders (progressive brain disease, epilepsy secondary to progressive cerebral lesion)
• Known second or third degree atrioventricular (AV) block
• History of status epilepticus within the 3 months prior to enrolment
• Seizures of non-epileptic origin (e.g. metabolic or neoplastic, or related to active infection)
• Lennox-Gastaut syndrome
• West syndrome
• Major psychiatric disorders
• Previous treatment in any study with Eslicarbazepine Acetate
• Pregnancy
• Breast-feeding
• History of hypersensitiviti to the investigational products or to drugs with similar chemical structures
• Impaired renal function, as shown by creatinine clearance values <60mL/min at screening
• Any other clinically significant abnormal laboratory finding at screening
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
• Inadequate completion of the study diaries during the baseline period
• Inadequate completation with study requirements during the baseline period
• Participation in a clinical trial within the last 2 months

E.5 End points

E.5.1

Primary end point(s)

Two primary variables with the following hierarchical order are defined:
1. Responder rate, defined as the proportion of patients with at least a 50% decrease in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period.
2. Relative reduction in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part I: • Baseline period (8 weeks scheduled): between Visit V1 (screening visit) and first intake of double-blind study medication at Visit V2
• Titration period (6 weeks scheduled): between first intake of double-blind study medication at Visit V2 and Visit V4
• Maintenance period (12 weeks scheduled): between intake of study medication at Visit V4 and Visit V7
• Tapering-off /follow-up period (4 8 weeks scheduled): between Visit V7 and Visit FU1
Part II: please refer to protocol and amendments.

E.5.2

Secondary end point(s)

• To assess the safety and tolerability of Eslicarbazepine Acetate as adjunctive therapy in children and adolescents with refractory partial seizures
• To assess the proportion of seizure-free patients and of patients with more than 75% reduction in seizure frequency
• To assess the frequency of patients with exacerbations
• To assess the duration of seizures and severity of seizures (using the Hague seizure severity scale)
• To assess the potential for rebound effects and withdrawal phenomena
• To assess the potential for interactions between Eslicarbazepine Acetate and concomitant AED medication
• To assess the seizure frequency by seizure type
• To assess the maintenance of the therapeutic effect of Eslicarbazepine Acetate during long-term treatment in Part II of the study

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

Yes

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)

E.8.2.2

Placebo

Yes

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

Austria

Bosnia and Herzegovina

Czech Republic

France

Germany

Hungary

Italy

Poland

Portugal

Romania

Russian Federation

Serbia

Slovakia

Spain

Ukraine

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

The end of the study is defined as the date of the last visit for the last patient to complete the study (including 14 days for AE reporting).

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

Yes

F.1.1

Number of subjects for this age range:

230

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

150

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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 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 2007-07-09.

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

240

F.4.2.2

In the whole clinical trial

315

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)

the test substance will be tapered-off subsequently and will be replaced by a standard anti-epileptic medication, the investigator will remain the primary treating physician and the first contact person of the patients

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

2007-09-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-08-24

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