Partial EpilepsyPhase 2NCT01527513
Effects of Eslicarbazepine Acetate (Esl, Bia 2-093) on Cognitive Function in Children With Partial Onset Seizures
A Phase 2 study testing Eslicarbazepine acetate (BIA 2-093) in people with Partial Epilepsy, run by Bial - Portela C S.A. at 36 sites in 5 countries.
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. Read more about this study
- Who is it for?
- Ages 6 to 16 years
- Conditions the study is for
- Partial Epilepsy
- What is being tested?
- Eslicarbazepine acetate (BIA 2-093)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 36 sitesin 5 countries
- Study dates
- Aug 2010to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
36 sites in 5 countries.
36 sites in 5 countries
Italy11 sites
Ospedale Salesi
Ancona, 60123
Ospedale Pediatrico Giovanni XXII
Bari, 70126
Ospedale Maggiore "C.A. Pizzardi"
Bologna, 40133
Istituto Scientifico G. Gaslini
Genova, 16146
Ospedale Carlo Poma
Mantua, 46100
Policlinico Martino
Messina, 98128
Ospedale Fatebenefratelli
Milan, 20121
Policlinico Seconda Università di Napoli
Naples, 80131
Istituto Mondino
Pavia, 27100
Ospedale Bambin Gesu
Roma, 00165
Azienda Ospedaliera O.I.R.M.- Sant'Anna
Torino, 10126
Russia11 sites
State Medical Institution "Children Republic Clinical Hospital of Minzdrav of Republic Tatarstan"
Kazan', 420138
Moscow State Healthcare Institution Scientific and Practical centre of medical help to children
Moscow, 119620
State Institution "Moscow Regional Scientific and Research Clinical Institute named after M.F. Vladimirsky"
Moscow, 129110
OOO City Neurological Center "Sibneuromed"
Novosibirsk, 630091
Saint Petersburg Scientific and Research Psycho-Neurology Institute
Saint Petersburg, 192019
Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social development of Russian Federation
Saint Petersburg, 194100
Saint-Petersburg State Pediatric Medical Academy of Ministry of Health and Social
Saint Petersburg, 194100
Institution Russian Academy of Science Institute of human brain RAN
Saint Petersburg, 197376
Saint-Petersburg Sate Healthcare Institution "Children City Hospital #1"
Saint Petersburg, 198205
State Healthcare Institution "Samarskaya Regional Clinical Hosptital named after M.I.Kalinin"
Samara, 443095
Yaroslavskay State Medical Academy of Roszdrav
Yaroslavl, 150030
Ukraine7 sites
Donetsk Region Child Clinical Centre of Neuroreabilitation
Donetsk, 83052
Regional psycho-neurological hospital #3
Ivano-Frankivsk, 76014
chair of neuropathology and pediatric neurology of Kharkov Medical Academy
Kharkiv, 61018
Danylo Galytskyy Lviv National Medical University
Lviv, 79010
Communal institution "Child City Hospital #3"
Odesa, 65125
Vinnytsya National Medical University,Vinnytsya Regional Psychoneurological Hospital
Vinnitsa, 21005
Zaporizhya regional clinical children hospital
Zaporizhzhya, 69063
Poland5 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Gabinet Lekarski Neurologii Dzieciecej i Leczenia Padaczki
Kielce, 25-316
Wielkopolskie Centrum Neurologii Dzieci i Mlodziezy
Poznan, 60-311
AKADEMIA MEDYCZNA im. Karola Marcinkowskiego w Poznaniu Katedra I Klinika Neurologii Wieku Rozwojowego
Poznan, 60-355
Instytut "Pomnik-Centrum Zdrowia Dziecka"
Warsaw, 04-730
Netherlands2 sites
Amphia Ziekenhuis
Breda, 4819 EV
Kempenhaeghe, location Heeze
Heeze, 5591 VE
About this study
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
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.
Read the 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
- Being tested
- Eslicarbazepine acetate (BIA 2-093), Placebo
- Keywords
- Partial Epilepsy, eslicarbazepine acetate, Children
- Medical subject headings
- Epilepsies, Partial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eslicarbazepine acetate (BIA 2-093)Drug
Also called Eslicarbazepine acetate
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.
PlaceboDrug
Treatments will be administered by oral route, once-daily, in the evening.
| Study group | Role | What they receive |
|---|---|---|
| Eslicarbazepine acetate (BIA 2-093) | Experimental | Not described Receives: Drug: Eslicarbazepine acetate (BIA 2-093) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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 (2)
Change From Baseline in Standardized Seizure Frequency - Part I
Measured: Baseline; Titration Period (4 Weeks: V2-V3-V4)
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
Measured: Weeks 1 to ≥ 41 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2012 (estimated)
- Study startAug 2010
- Primary completionMar 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Partial EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01527513
- Sponsor's protocol ID
- BIA-2093-208
- Status last verified
- Oct 2014
- First submitted
- 3 Feb 2012
- Last updated
- 24 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31878820
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01527513
- Acronym / sponsor ID
- BIA-2093-208
- Conditions
- Partial Epilepsy
- Keywords
- Partial Epilepsy, eslicarbazepine acetate, Children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- Aug 2010
- Primary completion
- Mar 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 7 Feb 2012 (estimated)
- Results
- Posted 24 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eslicarbazepine acetate (BIA 2-093) | Experimental | Drug: Eslicarbazepine acetate (BIA 2-093) |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 6 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (16 listed)
- 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;
Key exclusion criteria (25 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eslicarbazepine acetate (BIA 2-093)Also: Eslicarbazepine acetateEslicarbazepine 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. | Drug | Eslicarbazepine acetate (BIA 2-093) |
| PlaceboTreatments will be administered by oral route, once-daily, in the evening. | Drug | Placebo |
Primary outcome
Change From Baseline in Power of Attention Score to the End of the Double Blind (DB) Period
Time frame: Visit 1 (-4 weeks for training), Visit 2 (Day 1), Visit 5 (6 weeks), Visit 7 (12 weeks) or at early discontinuation visit (EDV)
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)
2 secondary outcomes
Change From Baseline in Standardized Seizure Frequency - Part I
Time frame: Baseline; Titration Period (4 Weeks: V2-V3-V4)
Change From Baseline in Seizure Frequency During the One-year Open-Label (OL)
Time frame: Weeks 1 to ≥ 41 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31878820Mintz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
36 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eslicarbazepine acetate (BIA 2-093) in people with Partial Epilepsy, run by Bial - Portela C S.A. at 36 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in Italy, Russia, Ukraine, Poland, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Power of Attention Score to the End of the Double Blind (DB) Period (time frame: Visit 1 (-4 weeks for training), Visit 2 (Day 1), Visit 5 (6 weeks), Visit 7 (12 weeks) or at early discontinuation visit (EDV)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01527513, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2014.