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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01527513
First received: February 3, 2012
Last updated: November 29, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Partial Epilepsy
Drug: Eslicarbazepine acetate (BIA 2-093)
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Bial - Portela C S.A.:

Primary Outcome Measures:
  • effects of eslicarbazepine acetate on cognition [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    Change from baseline to the end of the evaluation period in the composite Power of Attention measure in order to assess information processing speed and attention / psychomotor speed.

    Changes from baseline in Power of Attention will be compared between the treatment groups using an analysis of covariance (ANCOVA). The primary analysis will be on the PP population. Analysis on the intent-to-treat (ITT) population will be supportive.



Secondary Outcome Measures:
  • tolerability [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Treatment-emergent adverse events (TEAEs)

  • efficacy [ Time Frame: 8 week ] [ Designated as safety issue: Yes ]
    Relative reduction from baseline in seizure frequency over the evaluation period as compared with placebo;

  • Safety [ Time Frame: 8 Weeks ] [ Designated as safety issue: Yes ]
    Treatment-emergent adverse events (TEAEs)


Estimated Enrollment: 117
Study Start Date: November 2007
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eslicarbazepine acetate (BIA 2-093) Drug: Eslicarbazepine acetate (BIA 2-093)
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.
Other Name: Eslicarbazepine acetate
Placebo Comparator: Placebo Drug: Placebo
Treatments will be administered by oral route, once-daily, in the evening.

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

Ages Eligible for Study:   6 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01527513

Locations
Italy
Ospedale Salesi
Ancona, Italy, 60123
Ospedale Pediatrico Giovanni XXII
Bari, Italy, 70126
Ospedale Maggiore "C.A. Pizzardi"
Bologna, Italy, 40133
Istituto Scientifico G. Gaslini
Genova, Italy, 16146
Ospedale Carlo Poma
Mantova, Italy, 46100
Policlinico Martino
Messina, Italy, 98128
Ospedale Fatebenefratelli
Milano, Italy, 20121
Policlinico Seconda Università di Napoli
Napoli, Italy, 80131
Istituto Mondino
Pavia, Italy, 27100
Ospedale Bambin Gesu
Roma, Italy, 00165
Azienda Ospedaliera O.I.R.M.- Sant'Anna
Torino, Italy, 10126
Netherlands
Amphia Ziekenhuis
Breda, Netherlands, 4819 EV
Kempenhaeghe, location Heeze
Heeze, Netherlands, 5591 VE
Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland, 80-952
Gabinet Lekarski Neurologii Dzieciecej i Leczenia Padaczki
Kielce, Poland, 25-316
AKADEMIA MEDYCZNA im. Karola Marcinkowskiego w Poznaniu Katedra I Klinika Neurologii Wieku Rozwojowego
Poznan, Poland, 60-355
Wielkopolskie Centrum Neurologii Dzieci i Mlodziezy
Poznan, Poland, 60-311
Instytut "Pomnik-Centrum Zdrowia Dziecka"
Warszawa, Poland, 04-730
Russian Federation
State Medical Institution "Children Republic Clinical Hospital of Minzdrav of Republic Tatarstan"
Kazan, Russian Federation, 420138
State Institution "Moscow Regional Scientific and Research Clinical Institute named after M.F. Vladimirsky"
Moscow, Russian Federation, 129110
Moscow State Healthcare Institution Scientific and Practical centre of medical help to children
Moscow, Russian Federation, 119620
OOO City Neurological Center "Sibneuromed"
Novosibirsk, Russian Federation, 630091
Institution Russian Academy of Science Institute of human brain RAN
Saint Petersburg, Russian Federation, 197376
Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social development of Russian Federation
Saint-Petersburg, Russian Federation, 194100
Saint-Petersburg Sate Healthcare Institution "Children City Hospital #1"
Saint-Petersburg, Russian Federation, 198205
State Healthcare Institution "Samarskaya Regional Clinical Hosptital named after M.I.Kalinin"
Samara, Russian Federation, 443095
Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social
St. Petersburg, Russian Federation, 194100
Saint Petersburg Scientific and Research Psycho-Neurology Institute
St.-Petersburg, Russian Federation, 192019
Yaroslavskay State Medical Academy of Roszdrav
Yaroslavl, Russian Federation, 150030
Ukraine
Donetsk Region Child Clinical Centre of Neuroreabilitation
Donetsk, Ukraine, 83052
Regional psycho-neurological hospital #3
Ivano-Frankivsk, Ukraine, 76014
chair of neuropathology and pediatric neurology of Kharkov Medical Academy
Kharkov, Ukraine, 61018
Danylo Galytskyy Lviv National Medical University
Lviv, Ukraine, 79010
Communal institution "Child City Hospital #3"
Odesa, Ukraine, 65125
Vinnytsya National Medical University,Vinnytsya Regional Psychoneurological Hospital
Vinnitsa, Ukraine, 21005
Zaporizhya regional clinical children hospital
Zaporozhye, Ukraine, 69063
Sponsors and Collaborators
Bial - Portela C S.A.
  More Information

No publications provided

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01527513     History of Changes
Other Study ID Numbers: BIA-2093-208
Study First Received: February 3, 2012
Last Updated: November 29, 2013
Health Authority: Poland: Ministry of Health

Keywords provided by Bial - Portela C S.A.:
Partial Epilepsy
eslicarbazepine acetate
Children

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Eslicarbazepine acetate
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 11, 2014