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

Partial Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01527513
• Other study ID #: BIA-2093-208
• Status: Completed
• Phase: Phase 2
• First received: February 3, 2012
• Last updated: October 23, 2014
• Start date: August 2010
• Est. completion date: May 2013

Study information

• Verified date: October 2014
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: May 2013
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 16 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsies, Partial
• Partial Epilepsy

Intervention

Drug:
• 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.
• Placebo
Treatments will be administered by oral route, once-daily, in the evening.

Locations

Country	Name	City	State
Italy	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	Milano
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
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Kempenhaeghe, location Heeze	Heeze
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Gabinet Lekarski Neurologii Dzieciecej i Leczenia Padaczki	Kielce
Poland	AKADEMIA MEDYCZNA im. Karola Marcinkowskiego w Poznaniu Katedra I Klinika Neurologii Wieku Rozwojowego	Poznan
Poland	Wielkopolskie Centrum Neurologii Dzieci i Mlodziezy	Poznan
Poland	Instytut "Pomnik-Centrum Zdrowia Dziecka"	Warszawa
Russian Federation	State Medical Institution "Children Republic Clinical Hospital of Minzdrav of Republic Tatarstan"	Kazan
Russian Federation	Moscow State Healthcare Institution Scientific and Practical centre of medical help to children	Moscow
Russian Federation	State Institution "Moscow Regional Scientific and Research Clinical Institute named after M.F. Vladimirsky"	Moscow
Russian Federation	OOO City Neurological Center "Sibneuromed"	Novosibirsk
Russian Federation	Institution Russian Academy of Science Institute of human brain RAN	Saint Petersburg
Russian Federation	Saint-Petersburg Sate Healthcare Institution "Children City Hospital #1"	Saint-Petersburg
Russian Federation	Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social development of Russian Federation	Saint-Petersburg
Russian Federation	State Healthcare Institution "Samarskaya Regional Clinical Hosptital named after M.I.Kalinin"	Samara
Russian Federation	Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social	St. Petersburg
Russian Federation	Saint Petersburg Scientific and Research Psycho-Neurology Institute	St.-Petersburg
Russian Federation	Yaroslavskay State Medical Academy of Roszdrav	Yaroslavl
Ukraine	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	Kharkov
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	Zaporozhye

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Countries where clinical trial is conducted

Italy,  Netherlands,  Poland,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Power of Attention Score to the End of the Double Blind (DB) Period	Power of Attention was defined as the sum of the reaction time measures from the attentional tasks (simple [dominant hand only] reaction time, choice reaction time and digit vigilance speed) in order to assess information processing speed and attention/psychomotor speed.Change from baseline to the end of the double-blind period in Power of Attention will be compared between the treatment groups using an ANCOVA. Non-inferiority of ESL vs Placebo will be assessed by comparing the 95% CI's upper bound of the difference of Least Squares Mean (LSmeans) between treatment groups (ESL-placebo) with 121 ms. If the upper bound is greater than 121 ms then the null hypothesis that the change from baseline in the Power of Attention score in ESL group is at least 121 ms inferior than the placebo group will be rejected. Single Values were calculated the average of post treatment visits (visits 5 and 7or EDV) minus average of baseline visits (visits 1 and 2)	Visit 1 (-4 weeks for training), Visit 2 (Day 1), Visit 5 (6 weeks), Visit 7 (12 weeks) or at early discontinuation visit (EDV)	No
Secondary	Change From Baseline in Standardized Seizure Frequency - Part I		Baseline; Titration Period (4 Weeks: V2-V3-V4)	No
Secondary	Change From Baseline in Seizure Frequency During the One-year Open-Label (OL)	Overall Change from Baseline in Seizure Frequency per week for the One-Year Open-Label Period	Weeks 1 to = 41 weeks	No