Effects of Eslicarbazepine Acetate (Esl, Bia 2-093) on Cognitive Function in Children With Partial Onset Seizures

NCT ID: NCT01527513

Last Updated: 2014-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2013-05-31

Brief Summary

To evaluate the effects of eslicarbazepine acetate on cognition in comparison with placebo as adjunctive therapy in children aged 6 to 16 years old with refractory partial-onset seizures.

Detailed Description

This will be a 2-part multicentre study in approximately 117 patients. Part I of the study will consist of a 4-week prospective observational baseline period, a 12-week double-blind period (4-week up-titration and 8-week maintenance), and a tapering-off period.

After the screening visit (V1), patients will enter the baseline period. At the end of the baseline period (V2), eligible patients will be randomised in a ratio of 2:1 to receive double-blind treatment with Eslicarbazepine acetate or Placebo in addition to concomitant therapy with 1 or 2 Anti-Epileptic Drugs (AEDs). Concomitant AED therapy will be kept stable during the whole study.

Initial dose of the study treatment will be 10 mg/kg/day. After 2-weeks on 10 mg/kg/day, the dose will be up-titrated to 20 mg/kg/day (maximum 1200 mg/day). After 2 weeks on 20 mg/kg/day, dose will be up-titrated to 30 mg/kg/day (maximum 1200 mg/day) and patients will receive this dose for 8 weeks. If intolerable adverse events (AEs) occur, the patient can be down-titrated to the previous dose (only 1 down-titration step will be allowed) or discontinued. After the 8-week maintenance period, the study treatment will be tapered off in 10 mg/kg/day 2 week steps. However, if a patient experiences an increase in seizure frequency (e.g. more than 100% increase vs. baseline) during tapering-off, the patient can proceed directly to the open-label part of the study (Part II).

After completion of the last 2-week 10 mg/kg/day step, patients will have the option to enter a 1 year open-label treatment (Part II) with Eslicarbazepine acetate (up to 30 mg/kg/day, maximum 1200 mg/day), or will have a 4 week observational follow-up period.

Conditions

Partial Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Eslicarbazepine acetate (BIA 2-093)

Group Type: EXPERIMENTAL

Eslicarbazepine acetate (BIA 2-093)

Intervention Type: DRUG

Eslicarbazepine acetate (ESL) tablets 200 mg and the matching placebo will be supplied. Treatments will be administered by oral route, once-daily, in the evening. The dose will be rounded to the nearest 100 mg unit. Half tablets may be used for dose adjustment if necessary.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Treatments will be administered by oral route, once-daily, in the evening.

Interventions

Eslicarbazepine acetate (BIA 2-093)

Eslicarbazepine acetate (ESL) tablets 200 mg and the matching placebo will be supplied. Treatments will be administered by oral route, once-daily, in the evening. The dose will be rounded to the nearest 100 mg unit. Half tablets may be used for dose adjustment if necessary.

Intervention Type: DRUG

Placebo

Treatments will be administered by oral route, once-daily, in the evening.

Intervention Type: DRUG

Other Intervention Names

Eslicarbazepine acetate

Eligibility Criteria

Inclusion Criteria

At visit 1 (screening), patient must be/have:

• written informed consent by parent or legal guardian and, where applicable, the patient;
• age 6 to 16 years, inclusive;
• a documented diagnosis of epilepsy for at least 12 months prior to screening;
• at least 2 partial onset seizures during the 4 weeks prior to screening despite treatment with 1 to 2 AEDs in a stable dose regimen;
• an Intelligence Quotient (IQ) of at least 70;
• current treatment with 1 to 2 AEDs (except oxcarbazepine, benzodiazepines other than clobazam and vagus nerve stimulation (VNS));
• excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and clinical laboratory tests;
• in the opinion of the investigator, able to complete the Cognitive Drug Research (CDR) test battery;
• in case of a girl of childbearing potential, patient presents a serum B-human chorionic gonadotropin (B hCG) test consistent with a non gravid state and agrees to remain abstinent or use reliable contraception (if used, hormonal contraception must be combined with a barrier method) starting at screening and continuing until at least the post-study visit (PSV).

At visit 2 (randomisation), patient must be/have:

• at least 2 partial-onset seizures during the 4 week baseline period prior to randomisation (documented in a diary);
• in case of a girl of childbearing potential, patient presents a urine B-hCG test consistent with a non-gravid state;
• stable dose regimen of concomitant AEDs during the 4 week baseline period;
• diaries satisfactorily completed by the patient or his/her caregiver during the baseline period;
• satisfactory compliance with the study requirements during the baseline period.

Exclusion Criteria

At visit 1 (screening), patients must not be/have:

• only simple partial seizures with no motor symptomatology;
• primarily generalised seizures;
• known rapidly progressive neurological disorders (progressive brain disease, epilepsy secondary to progressive cerebral lesion);
• occurrence of seizures too close to count accurately;
• history of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months prior to screening; seizures of non-epileptic origin;
• Lennox-Gastaut syndrome;
• West syndrome;
• major psychiatric disorders;
• seizures of psychogenic origin within the last 2 years;
• history of schizophrenia or suicide attempt;
• history of attention deficit disorder or other diseases adversely affecting cognitive abilities;
• currently treated with oxcarbazepine, benzodiazepines other than clobazam (on a routine or chronic basis) and/or VNS;
• known hypersensitivity to carboxamide derivatives (oxcarbazepine or carbamazepine);
• uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder;
• second or third degree atrioventricular blockade;
• relevant clinical laboratory abnormalities;
• estimated creatinine clearance (CLCR) <60 mL/min;
• pregnancy or nursing;
• treatment with eslicarbazepine acetate in any previous study;
• participation in other drug clinical trial within the last 2 months;
• not ensured capability to perform the trial;
• any other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol.

At visit 2 (randomisation), patients must not be / have:

• any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bial - Portela C S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ospedale Salesi

Ancona, , Italy

Ospedale Pediatrico Giovanni XXII

Bari, , Italy

Ospedale Maggiore "C.A. Pizzardi"

Bologna, , Italy

Istituto Scientifico G. Gaslini

Genova, , Italy

Ospedale Carlo Poma

Mantova, , Italy

Policlinico Martino

Messina, , Italy

Ospedale Fatebenefratelli

Milan, , Italy

Policlinico Seconda Università di Napoli

Napoli, , Italy

Istituto Mondino

Pavia, , Italy

Ospedale Bambin Gesu

Roma, , Italy

Azienda Ospedaliera O.I.R.M.- Sant'Anna

Torino, , Italy

Amphia Ziekenhuis

Breda, , Netherlands

Kempenhaeghe, location Heeze

Heeze, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Gabinet Lekarski Neurologii Dzieciecej i Leczenia Padaczki

Kielce, , Poland

Wielkopolskie Centrum Neurologii Dzieci i Mlodziezy

Poznan, , Poland

AKADEMIA MEDYCZNA im. Karola Marcinkowskiego w Poznaniu Katedra I Klinika Neurologii Wieku Rozwojowego

Poznan, , Poland

Instytut "Pomnik-Centrum Zdrowia Dziecka"

Warsaw, , Poland

State Medical Institution "Children Republic Clinical Hospital of Minzdrav of Republic Tatarstan"

Kazan', , Russia

Moscow State Healthcare Institution Scientific and Practical centre of medical help to children

Moscow, , Russia

State Institution "Moscow Regional Scientific and Research Clinical Institute named after M.F. Vladimirsky"

Moscow, , Russia

OOO City Neurological Center "Sibneuromed"

Novosibirsk, , Russia

Saint Petersburg Scientific and Research Psycho-Neurology Institute

Saint Petersburg, , Russia

Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social development of Russian Federation

Saint Petersburg, , Russia

Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social

Saint Petersburg, , Russia

Institution Russian Academy of Science Institute of human brain RAN

Saint Petersburg, , Russia

Saint-Petersburg Sate Healthcare Institution "Children City Hospital #1"

Saint Petersburg, , Russia

State Healthcare Institution "Samarskaya Regional Clinical Hosptital named after M.I.Kalinin"

Samara, , Russia

Yaroslavskay State Medical Academy of Roszdrav

Yaroslavl, , Russia

Donetsk Region Child Clinical Centre of Neuroreabilitation

Donetsk, , Ukraine

Regional psycho-neurological hospital #3

Ivano-Frankivsk, , Ukraine

chair of neuropathology and pediatric neurology of Kharkov Medical Academy

Kharkiv, , Ukraine

Danylo Galytskyy Lviv National Medical University

Lviv, , Ukraine

Communal institution "Child City Hospital #3"

Odesa, , Ukraine

Vinnytsya National Medical University,Vinnytsya Regional Psychoneurological Hospital

Vinnitsa, , Ukraine

Zaporizhya regional clinical children hospital

Zaporizhzhya, , Ukraine

Countries

Italy; Netherlands; Poland; Russia; Ukraine

References

Mintz M, Pina-Garza JE, Wolf SM, McGoldrick PE, Jozwiak S, Grinnell T, Cantu D, Costa R, Moreira J, Li Y, Blum D. Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (Aged 4-17 Years) With Focal Seizures. J Child Neurol. 2020 Mar;35(4):265-273. doi: 10.1177/0883073819890997. Epub 2019 Dec 26.

Reference Type: DERIVED

PMID: 31878820 (View on PubMed)

Other Identifiers

BIA-2093-208

Identifier Type: -

Identifier Source: org_study_id