Clinical trial NCT01527513: Effects of Eslicarbazepine Acetate (Esl, Bia 2-093) on Cognitive Function in Children With Partial Onset Seizures
Official title: Effects of Eslicarbazepine Acetate (Esl, Bia 2-093) on Cognitive Function in Children With Partial Onset Seizures: an add-on, Double-blind, Randomised, Placebo-controlled, Parallel Group, Multicentre Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Partial Epilepsy
Keywords: Partial Epilepsy
eslicarbazepine acetate
Children
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2012-02-07
Enrollment: 123
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Power of Attention Score to the End of the Double Blind (DB) Period
timeFrame: Visit 1 (-4 weeks for training), Visit 2 (Day 1), Visit 5 (6 weeks), Visit 7 (12 weeks) or at early discontinuation visit (EDV)
Secondary outcomes:
measure: Change From Baseline in Standardized Seizure Frequency - Part I
timeFrame: Baseline; Titration Period (4 Weeks: V2-V3-V4)
measure: Change From Baseline in Seizure Frequency During the One-year Open-Label (OL)
timeFrame: Weeks 1 to ≥ 41 weeks
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedale Salesi
city: Bari
country: Italy
facility: Ospedale Pediatrico Giovanni XXII
city: Bologna
country: Italy
facility: Ospedale Maggiore "C.A. Pizzardi"
city: Genova
country: Italy
facility: Istituto Scientifico G. Gaslini
city: Mantova
country: Italy
facility: Ospedale Carlo Poma
city: Messina
country: Italy
facility: Policlinico Martino
city: Milano
country: Italy
facility: Ospedale Fatebenefratelli
city: Napoli
country: Italy
facility: Policlinico Seconda Università di Napoli
city: Pavia
country: Italy
facility: Istituto Mondino
city: Roma
country: Italy
facility: Ospedale Bambin Gesu
city: Torino
country: Italy
facility: Azienda Ospedaliera O.I.R.M.- Sant'Anna
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Heeze
country: Netherlands
facility: Kempenhaeghe, location Heeze
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Kielce
country: Poland
facility: Gabinet Lekarski Neurologii Dzieciecej i Leczenia Padaczki
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Neurologii Dzieci i Mlodziezy
city: Poznan
country: Poland
facility: AKADEMIA MEDYCZNA im. Karola Marcinkowskiego w Poznaniu Katedra I Klinika Neurologii Wieku Rozwojowego
city: Warszawa
country: Poland
facility: Instytut "Pomnik-Centrum Zdrowia Dziecka"
city: Kazan
country: Russian Federation
facility: State Medical Institution "Children Republic Clinical Hospital of Minzdrav of Republic Tatarstan"
city: Moscow
country: Russian Federation
facility: Moscow State Healthcare Institution Scientific and Practical centre of medical help to children
city: Moscow
country: Russian Federation
facility: State Institution "Moscow Regional Scientific and Research Clinical Institute named after M.F. Vladimirsky"
city: Novosibirsk
country: Russian Federation
facility: OOO City Neurological Center "Sibneuromed"
city: Saint Petersburg
country: Russian Federation
facility: Institution Russian Academy of Science Institute of human brain RAN
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social development of Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg Sate Healthcare Institution "Children City Hospital #1"
city: Samara
country: Russian Federation
facility: State Healthcare Institution "Samarskaya Regional Clinical Hosptital named after M.I.Kalinin"
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social
city: St.-Petersburg
country: Russian Federation
facility: Saint Petersburg Scientific and Research Psycho-Neurology Institute
city: Yaroslavl
country: Russian Federation
facility: Yaroslavskay State Medical Academy of Roszdrav
city: Donetsk
country: Ukraine
facility: Donetsk Region Child Clinical Centre of Neuroreabilitation
city: Ivano-Frankivsk
country: Ukraine
facility: Regional psycho-neurological hospital #3
city: Kharkov
country: Ukraine
facility: chair of neuropathology and pediatric neurology of Kharkov Medical Academy
city: Lviv
country: Ukraine
facility: Danylo Galytskyy Lviv National Medical University
city: Odesa
country: Ukraine
facility: Communal institution "Child City Hospital #3"
city: Vinnitsa
country: Ukraine
facility: Vinnytsya National Medical University,Vinnytsya Regional Psychoneurological Hospital
city: Zaporozhye
country: Ukraine
facility: Zaporizhya regional clinical children hospital
Study officials:
References:
citation: 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.