Refractory Partial EpilepsyPhase 3NCT00957684
Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures
A Phase 3 study testing eslicarbazepine acetate in people with Refractory Partial Epilepsy, run by Bial - Portela C S.A. at 1 site in Portugal.
Trial summary
This was a phase III 4-part study in multiple centres. Part I was a 26-week parallel-group, randomised, placebo-controlled period (8 weeks single-blind placebo baseline, 2 weeks double-blind titration, 12 weeks maintenance, and 4 weeks tapering off). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Partial Epilepsy
- What is being tested?
- eslicarbazepine acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 402 participants
- Where
- 1 sitePortugal
- Study dates
- Jul 2004to Feb 2007
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent signed by patient
- aged 18 years or more
- documented diagnosis of simple or complex partial seizures with or without secondary generalisation since at least 12 months prior to screening
- at least 4 partial seizures in each 4 week period during the last 8 weeks prior to screening, currently treated with 1 or 2 AEDs (any except oxcarbazepine and felbamate), in a stable dose regimen during at least 2 months prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified)
- excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and laboratory tests
- post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of woman of childbearing potential, patient must present a serum beta-hCG test consistent with a non-gravid state and agree to remain abstinent or use reliable contraception (oral contraception should be combined with a barrier method)
Who cannot join
- only simple partial seizures with no motor symptomatology (classified as A2-4 according to the International Classification of Epileptic Seizures) that are not video-EEG documented
- primarily generalised epilepsy
- known rapid progressive neurological disorder; 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 psychogenic origin within the last 2 years
- history of schizophrenia or suicide attempt
- currently on or with exposure to felbamate or oxcarbazepine more within one month of screening
Show all 13Show fewer
- using benzodiazepines on more than on an occasional basis (except when used chronically as AED)
- previous use of ESL or participation in a clinical study with ESL
- known hypersensitivity to carbamazepine, oxcarbazepine or chemically related substances
- history of abuse of alcohol, drugs or medications within the last 2 years
- uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder
- second or third-degree atrioventricular blockade not corrected with a pacemaker
- relevant clinical laboratory abnormalities
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial.
This was a phase III 4-part study in multiple centres. Part I was a 26-week parallel-group, randomised, placebo-controlled period (8 weeks single-blind placebo baseline, 2 weeks double-blind titration, 12 weeks maintenance, and 4 weeks tapering off). After completing the baseline period, patients were randomised in a 1:1:1:1 ratio to 1 of 3 ESL dose levels or to placebo. Part II was a 1-year open-label extension for patients who had completed Part I. The starting dose was 800 mg once daily and could be titrated up or down at 400-mg intervals between 400 and 1200 mg. Part III was an additional 1-year open-label extension for patients who had completed Part II, had participated in the post-Part II study extension, which allowed patients to continue treatment with ESL, or had continued to take ESL in a compassionate use program. ESL starting doses were the same as received at the end of Part II, during post-Part II study extension, or under compassionate use, and could be titrated up or down at 400-mg intervals between 400 and 1200 mg once daily. Part IV was a study extension to allow patients to continue ESL treatment after the end of Part III until marketing authorisation or discontinuation of clinical development.
Read the detailed description
Duration of Treatment: The duration of Part I was 26 weeks: 8 weeks of placebo run-in, 2 weeks of dose titration, 12 weeks of maintenance, and 4 weeks of tapering-off period. The duration of Part II was 1 year. The duration of Part III was planned to be 1 year (some patients were treated for >1 year). The duration of Part IV was >3 years (patients could continue treatment with ESL until market availability).
- Conditions
- Refractory Partial Epilepsy
- Being tested
- eslicarbazepine acetate, placebo
- Keywords
- refractory, partial, epilepsy
- Medical subject headings
- Epilepsies, Partial, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eslicarbazepine acetateDrug
Also called Zebinix
once-daily oral tablet
placeboDrug
once daily placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| ESL 400 mg once daily | Experimental | ESL was supplied in 400-mg and 800-mg tablets Receives: Drug: eslicarbazepine acetate |
| ESL 800 mg once daily | Experimental | ESL was supplied in 400-mg and 800-mg tablets Receives: Drug: eslicarbazepine acetate |
| ESL 1200 mg once daily | Experimental | ESL was supplied in 400-mg and 800-mg tablets Receives: Drug: eslicarbazepine acetate |
| placebo | Placebo comparator | Placebo matching tablets Receives: Drug: placebo |
| ESL - PART II | Experimental | During Part II of the study all patients received Eslicarbazepine Acetate (ESL), including those who had been treated with placebo during Part I. ESL was supplied as scored 800 mg tablets; once daily administration by oral route. Receives: Drug: eslicarbazepine acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part I: Seizure Frequency
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the intention-to-treat (ITT) population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment.to a "frequency per 4 weeks" basis
Measured: 12-week maintenance period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2009 (estimated)
- Study startJul 2004
- Primary completionNov 2005
- Study completionFeb 2007
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 Refractory 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 402 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Prof. Christian Elger, Principal investigator, Department of Epileptology, Friedrich Wilhelms University BonnProf. Peter Halasz, Principal investigator, National Institute of Psychiatry and Neurology, Budapest, Hungary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957684
- Sponsor's protocol ID
- BIA-2093-301
- Status last verified
- Mar 2025
- First submitted
- 10 Aug 2009
- Last updated
- 12 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Andermann E, Rosenfeld W, Penovich P, Rogin J, Cendes F, Carreno M, Ramsay RE, Ben-Menachem E, Gama H, Rocha F, Soares-da-Silva P, Tosiello R, Blum D, Grinnell T. Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (>/=60 years) and younger (18-59 years) adults. Epilepsy Res. 2021 Jan;169:106478. doi: 10.1016/j.eplepsyres.2020.106478. Epub 2020 Oct 10.
PubMed 33338829
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial.
- ClinicalTrials.gov ID
- NCT00957684
- Acronym / sponsor ID
- BIA-2093-301
- Conditions
- Refractory Partial Epilepsy
- Keywords
- refractory, partial, epilepsy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 402 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- Jul 2004
- Primary completion
- Nov 2005 (actual)
- Study completion
- Feb 2007 (actual)
- First posted
- 12 Aug 2009 (estimated)
- Results
- Posted 10 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a phase III 4-part study in multiple centres. Part I was a 26-week parallel-group, randomised, placebo-controlled period (8 weeks single-blind placebo baseline, 2 weeks double-blind titration, 12 weeks maintenance, and 4 weeks tapering off). After completing the baseline period, patients were randomised in a 1:1:1:1 ratio to 1 of 3 ESL dose levels or to placebo. Part II was a 1-year open-label extension for patients who had completed Part I. The starting dose was 800 mg once daily and could be titrated up or down at 400-mg intervals between 400 and 1200 mg. Part III was an additional 1-year open-label extension for patients who had completed Part II, had participated in the post-Part II study extension, which allowed patients to continue treatment with ESL, or had continued to take ESL in a compassionate use program. ESL starting doses were the same as received at the end of Part II, during post-Part II study extension, or under compassionate use, and could be titrated up or down at 400-mg intervals between 400 and 1200 mg once daily. Part IV was a study extension to allow patients to continue ESL treatment after the end of Part III until marketing authorisation or discontinuation of clinical development.
Detailed description
Duration of Treatment: The duration of Part I was 26 weeks: 8 weeks of placebo run-in, 2 weeks of dose titration, 12 weeks of maintenance, and 4 weeks of tapering-off period. The duration of Part II was 1 year. The duration of Part III was planned to be 1 year (some patients were treated for >1 year). The duration of Part IV was >3 years (patients could continue treatment with ESL until market availability).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| ESL 400 mg once daily | Experimental | Drug: eslicarbazepine acetateESL was supplied in 400-mg and 800-mg tablets |
| ESL 800 mg once daily | Experimental | Drug: eslicarbazepine acetateESL was supplied in 400-mg and 800-mg tablets |
| ESL 1200 mg once daily | Experimental | Drug: eslicarbazepine acetateESL was supplied in 400-mg and 800-mg tablets |
| placebo | Placebo comparator | Drug: placeboPlacebo matching tablets |
| ESL - PART II | Experimental | Drug: eslicarbazepine acetateDuring Part II of the study all patients received Eslicarbazepine Acetate (ESL), including those who had been treated with placebo during Part I. ESL was supplied as scored 800 mg tablets; once daily administration by oral route. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- written informed consent signed by patient
- aged 18 years or more
- documented diagnosis of simple or complex partial seizures with or without secondary generalisation since at least 12 months prior to screening
- at least 4 partial seizures in each 4 week period during the last 8 weeks prior to screening, currently treated with 1 or 2 AEDs (any except oxcarbazepine and felbamate), in a stable dose regimen during at least 2 months prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified)
- excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination and laboratory tests
Key exclusion criteria (13 listed)
- only simple partial seizures with no motor symptomatology (classified as A2-4 according to the International Classification of Epileptic Seizures) that are not video-EEG documented
- primarily generalised epilepsy
- known rapid progressive neurological disorder; 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 psychogenic origin within the last 2 years
- history of schizophrenia or suicide attempt
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 acetateAlso: Zebinixonce-daily oral tablet | Drug | ESL - PART II, ESL 1200 mg once daily, ESL 400 mg once daily, ESL 800 mg once daily |
| placeboonce daily placebo comparator | Drug | placebo |
Primary outcome
Part I: Seizure Frequency
Time frame: 12-week maintenance period
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the intention-to-treat (ITT) population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment.to a "frequency per 4 weeks" basis
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33338829Andermann E, Rosenfeld W, Penovich P, Rogin J, Cendes F, Carreno M, Ramsay RE, Ben-Menachem E, Gama H, Rocha F, Soares-da-Silva P, Tosiello R, Blum D, Grinnell T. Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (>/=60 years) and younger (18-59 years) adults. Epilepsy Res. 2021 Jan;169:106478. doi: 10.1016/j.eplepsyres.2020.106478. Epub 2020 Oct 10.
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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.
Prof. Christian Elger principal investigator
Department of Epileptology, Friedrich Wilhelms University Bonn
Prof. Peter Halasz principal investigator
National Institute of Psychiatry and Neurology, Budapest, Hungary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing eslicarbazepine acetate in people with Refractory Partial Epilepsy, run by Bial - Portela C S.A. at 1 site in Portugal.
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 6 inclusion and 13 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 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 10 Oct 2013). 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?
Part I: Seizure Frequency (time frame: 12-week maintenance period). 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 NCT00957684, 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 12 Mar 2025.