Partial EpilepsyPhase 3NCT00988429
Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures
A Phase 3 study testing 800 mg QD Eslicarbazepine acetate and 1200 mg QD Eslicarbazepine acetate in people with Partial Epilepsy, run by Bial - Portela C S.A. at 162 sites in 11 countries.
Trial summary
The purpose of this study is to determine whether Eslicarbazepine acetate (BIA 2-093) is an effective adjunct therapy in the treatment of refractory partial seizures Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Partial Epilepsy
- What is being tested?
- 800 mg QD Eslicarbazepine acetate and 1200 mg QD Eslicarbazepine acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 653 participants
- Where
- 162 sitesin 11 countries
- Study dates
- 2 Dec 2008to 12 Jan 2012
- Phase
- Phase 3
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- At V1 (screening), patient must be/have:
- Written informed consent signed by patient.
- Aged 16 years or more (patients under 18 years of age require parental/legal representative consent). In North America as well as in other participating countries, when appropriate and/or required by state or local law, minor patients must give written informed assent prior to participation in the study.
- A documented diagnosis of epilepsy since at least 12 months prior to screening.
- At least 4 partial-onset seizures (including subtypes of simple partial, complex partial and partial seizures evolving to secondarily generalised) on the 4 weeks prior to screening.
- Currently treated with 1 or 2 AEDs (any except OXC), in a stable dose regimen during at least 1 month prior to screening. Patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified (a confirmatory test should be available within 1 month before study entry). The device for VNS should be implanted at least 6 months before screening; parameters need to be stable for at least 1 month prior to screening (VNS will not be counted as concomitant AED).
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- Excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination findings, and clinical laboratory test results.
- Post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation. In case of women of childbearing potential (WOCBP), patient must present a serum beta-human chorionic gonadotropin (B-hCG) test consistent with a non gravid state and agree to remain abstinent or use reliable contraception (hormonal contraception should be combined with a barrier method) beginning at screening and continuing at least to the PSV.
- At V2 (randomisation), patient must have:
- At least 8 partial-onset seizures during baseline with at least 3 partial-onset seizures in each 4-week section of the 8-week baseline period prior to randomisation (documented in a diary) and no seizure-free interval exceeding 28 consecutive days.
- In case of WOCBP, patient must present a urine B-hCG test consistent with a non gravid state.
- Diaries satisfactorily completed by the patient or his/her caregiver.
- Satisfactorily complied with the study requirements during the baseline period (including no changes in concomitant AED therapy should have occurred in the baseline period).
Who cannot join
- At V1 (screening), patients must not be/have:
- Only simple partial seizures with no motor symptomatology (classified as A2 4 according to the International Classification of Epileptic Seizures).
- Primarily generalised seizures.
- Known 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.
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- Seizures of non-epileptic origin.
- Seizures of psychogenic origin within the last 2 years.
- Major psychiatric disorders.
- Documented diagnosis of schizophrenia with accompanying documented history of at least 1 acute psychosis episode within the last 2 years) or history of suicide attempt.
- Currently treated with OXC.
- Using benzodiazepines on more than an occasional basis (defined as more than 2 times per week), except when used chronically as AED.
- Known exposure to Eslicarbazepine acetate from previous study.
- o Previous use of Eslicarbazepine acetate or participation in a clinical study with Eslicarbazepine acetate (patients not exposed to Eslicarbazepine acetate [e.g., screen failed] are allowed).
- Known hypersensitivity to carboxamide derivatives.
- 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 (e.g., sodium <130 mmol/L, alanine or aspartate transaminases >2.0 times the upper limit of the normal, white blood cell [WBC] count <3,000 cells/mm3) or for patients of Asian ancestry, positive HLA B*1502 test.
- Estimated creatinine clearance <60 mL/min [men: (140-age) x weight/serum creatinine x 72; women: (0.85) (140-age) x weight/serum creatinine x 72. Age in years, weight in kg, and serum creatinine in mg/dL].
- Pregnant or nursing.
- Participation in other drug clinical trial within the last 2 months or received an investigational drug within 5 half-lives of this other product, whichever is longer. Patient(s) who are known to have not taken any doses of study drug(s) in earlier study(ies) (e.g. screen-failures) are allowed without any time limitation.
- 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.
- Currently treated with VNS, but implanted <6 months before screening or parameters not stable for at least 1 month prior to screening.
- At V2 (randomisation), patients must not be/have:
- Inadequate compliance to concomitant AEDs during the 8-week baseline period or to screening exclusion criteria.
- Inadequate completion of the study diary.
- Any other 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
162 sites in 11 countries.
162 sites in 11 countries
United States106 sites
Albany Medical College - Neurosciences Institute
Albany, New York, 12208
McFarland Clinic, PC
Ames, Iowa, 50010
University of Colorado Health Sciences
Aurora, Colorado, 80045
Kern County Neurological Medical Group, INC.
Bakersfield, California, 93301
University of Maryland Medical Center
Baltimore, Maryland, 21204
Johns Hopkins University
Baltimore, Maryland, 21287
Neurological Associates of Washington/Clinical Trials of America, Inc
Bellevue, Washington, 98004
Mid-Atlantic Epilepsy and Sleep Centre
Bethesda, Maryland, 20817
Consultants in Epilepsy and Neurology, PPLC
Boise, Idaho, 83702
MGH Epilepsy Service Massachusetts, General Hospital
Boston, Massachusetts, 02114
Bradenton Research Center
Bradenton, Florida, 34205
Private Practice of Dr. Edwin Green
Brownwood, Texas, 76801
The Cooper Health System
Camden, New Jersey, 08103
Five Towns Neuroscience Research
Cedarhurst, New York, 11516
The Neurological Institute, P.A.
Charlotte, North Carolina, 28204
University of Virginia - Comprehensive Epilepsy Program
Charlottesville, Virginia, 22903
The Comprehensive Epilepsy Care Centre for Chidren and Adults
Chesterfield, Missouri, 63017
Ohio State University Medical Centre
Columbus, Ohio, 43210
Arkansas Neurology
Conway, Arkansas, 72034
Texas Neurology, PA
Dallas, Texas, 75214
Neurology Consultants of Dallas, P.A.
Dallas, Texas, 75231
Neurological Clinic of Texas
Dallas, Texas, 75251
UTSWMC Department of Neurology, Division of Epilepsy Research
Dallas, Texas, 75390
Neurology Specialists, Inc
Dayton, Ohio, 45417
Denver Health
Denver, Colorado, 80204
Broadlawns Medical Center
Des Moines, Iowa, 50314
Medistat Clinical Research
DeSoto, Texas, 75115
Nemmar Clinical Resources
DeSoto, Texas, 75115
Wayne State University/Detroit Medical Center
Detroit, Michigan, 48201
Precise Research Centers
Flowood, Mississippi, 39232
Neuro-Pain Medical Center, Inc.
Fresno, California, 93710
Optima Neurological Services, LLC
Gainesville, Florida, 32608
University of Florida Department of Neurology
Gainesville, Florida, 32610
Clinical Research Centre of New Jersey
Gibbsboro, New Jersey, 08026
Minneapolis Clinic of Neurology, Ltd
Golden Valley, Minnesota, 55422
NW FL Clinical Research Group, LLC
Gulf Breeze, Florida, 32561
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
Palm Springs Research Institute
Hialeah, Florida, 33012
PMG Research of Hickory, LLC
Hickory, North Carolina, 28602
Houston Neurology and Sleep Center
Houston, Texas, 77063
Josephson Wallack Munshower Neurology P.C.
Indianapolis, Indiana, 46237
University of Florida
Jacksonville, Florida, 32209
University of Kentucky
Lexington, Kentucky, 40536
Clinical Trials Inc.
Little Rock, Arkansas, 72205
Neurological Care of CNY
Liverpool, New York, 13088
Loma Linda University
Loma Linda, California, 92354
Collaborative Neuroscience Network, INC
Long Beach, California, 90806
Dean & St. Mary's Outpatient Center Neurological Institute and Spine Center
Madison, Wisconsin, 53715
Marshfield Clinic
Marshfield, Wisconsin, 54449
Pharmax Research Clinic
Miami, Florida, 33126
Advanced Pharma CR, LLC
Miami, Florida, 33136
University of Miami - Miller School of Medicine Department of Neurology
Miami, Florida, 33136
Miami Children's Hospital
Miami, Florida, 33155
Neuroscience Consultants
Miami, Florida, 33176
Kendall South Medical Center, Inc.
Miami, Florida, 33185
Regional Epilepsy Centre of Aurora Healthcare- St. Luke's Medical Centre
Milwaukee, Wisconsin, 53215
Medical College of Wisconsin - Department of Neurology
Milwaukee, Wisconsin, 53226
University of South Alabama Department of Neurology
Mobile, Alabama, 36693
Viking Clinical Research Center
Murrieta, California, 92562
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
UMDNJ-Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
LSUHSC Epilepsy Center
New Orleans, Louisiana, 70112
Louisiana Research Associates, Inc.
New Orleans, Louisiana, 70114
Beth Israel Medical Center
New York, New York, 10003
NYU Comprehensive Epilepsy Centre
New York, New York, 10016
Wiell Cornell Medical Centre Epilepsy Centre
New York, New York, 10065
Sentara Medical Group, Neurology Specialists Sentara Heart Hospital
Norfolk, Virginia, 23507
Neurology Clinic, P.C.
Northport, Alabama, 35476
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112
Dent Neurologic Institute
Orchard Park, New York, 14127
St. Joseph Regional Medical Center
Paterson, New Jersey, 07503
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Comprehensive Epilepsy Center - Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Temple University School of Medicine - Department of Neurology
Philadelphia, Pennsylvania, 19140
21st Century Neurology - Division of Xenoscience, Inc.
Phoenix, Arizona, 85004
Barrow Neurological Institute / St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Phoenix Neurological Associates/Clinical Research Advantage
Phoenix, Arizona, 85018
Childrens Hospital of Pittsburg of UPMC - Division of Child Neurology
Pittsburgh, Pennsylvania, 15224
Medsol Clinical Research Center
Port Charlotte, Florida, 33952
Ranier Clinical Research Center
Renton, Washington, 98057
Strong Epilepsy Center - University of Rochester Medical Center
Rochester, New York, 14642
Harbin Clinic
Rome, Georgia, 30165
Minnesota Epilepsy Group, P.A.
Saint Paul, Minnesota, 55102
Wasatch Clinical Research
Salt Lake City, Utah, 84107
Innovative Clinical Trials
San Antonio, Texas, 78229
Road Runner Research
San Antonio, Texas, 78258
Bright Minds Institute
San Francisco, California, 94104
Milestone Clinical Research
San Jose, California, 95124
Lovelace Scientific Resources
Sarasota, Florida, 34233
University Washington Regional Epilepsy Center Harborview
Seattle, Washington, 98104
Southern Ilinois University School of Medicine
Springfield, Illinois, 62702
ANI Research, PC
Sun City, Arizona, 85351
SUNY Upstate Medical University
Syracuse, New York, 13210
MultiCare Adult Neurology
Tacoma, Washington, 98405
University of South Florida - Department of Neurology
Tampa, Florida, 33606
Pediatric Epilepsy & Neurology Specialists, PA
Tampa, Florida, 33609
Scott and White Memorial Hospital Sherwood and Brindley Foundation
Temple, Texas, 76508
Montefiore Medical Center
The Bronx, New York, 10467
University of Toledo - Health Science Campus
Toledo, Ohio, 43614
Shore Neurology, PA
Toms River, New Jersey, 08755
University of Arizona Health Sciences Center
Tucson, Arizona, 86724
Tulsa Clinical Reserch
Tulsa, Oklahoma, 74104
Lovelace Scientific Resources
Venice, Florida, 34292
Neurosearch II, Inc.
Ventura, California, 93003
Palm Beach Clinical Research Network, LLC.
Wellington, Florida, 33414
Wilmington Medical Research
Wilmington, North Carolina, 28401
Argentina10 sites
Hospital Privado de la comunidad de Mar de Plata
Buenos Aires, 7600
CEMIC
Buenos Aires
Centro Neurológico de Tratamiento y Rehabilitación
Buenos Aires
Hospital Italiano de Buenos Aires
Buenos Aires
Hospital Ramos Mejía
Capital Federal, 1221
Hospital Británico
Capital Federal, 1280
Fleni
Capital Federal, 1428
Instituto Médico Especializado (IME)
Capital Federal, 1428
Hospital Privado - Centro Médico de Córdoba S.A.
Córdoba, 5016
Centro de Neurologia y Neurorehabilitacion
Córdoba
Brazil10 sites
Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, MG30150-221
Hospital das Clínicas - UNICAMP
Campinas, SP13083-970
Instituto de Neurologia de Curitiba
Curitiba, PR81210-300
Hospital de Clínicas de Porto Alegre
Porto Alegre, RS90035-003
Hospital São Lucas - PUCRS
Porto Alegre, RS90610-000
Hospital das Clinicas da FMRP
Ribeirão Preto, SP14048-900
Faculdade de Medicina do ABC
Santo André, SP09060-650
Irmandade da Santa Casa de Misericórdia de São Paulo
São Paulo, SP01221-020
Hospital Brigadeiro
São Paulo, SP01401-901
Hospital São Paulo - UNIFESP
São Paulo, SP04039-032
France8 sites
CENTRE HOSPITALIER PELLEGRIN, CHU de BORDEAUX
Bordeaux, 33000
Hopital Femme-Mere-Enfant, Hospices Civils de Lyon
Bron, 69677 cedex
Hopital Roger Salengro, Chru de Lille
Lille, 59037
Hopital Gui de Chauliac, Chu de Montpellier
Montpellier, 34295
Hopital Central, Chu de Nancy
Nancy, 54035 cedex
Centre Hospitalier Sainte-Anne
Paris, 75014
Hopital Pontchaillou, Chru de Rennes
Rennes, 35033
Hopital Civil, Chru de Strasbourg
Strasbourg, 67091 cedex
Italy7 sites
Azienda Ospedaliero, Universitaria "Ospedali Riuniti", Clinica della Malattie del Sistema Nervoso, Università di Foggia
Foggia, 71100
A.O.U Policlinico di Messina
Messina, 98125
Università degli Studi di Napoli Policlinico Federico II
Naples, 80131
Azienda Ospedaliero - Universitaria Maggiore della Carità
Novara, 28100
Istituto Neurologico Casimiro Mondino
Pavia, 27100
Università Cattolica del Sacro Cuore Policlinico "A. Gemelli"
Roma, 00168
Azienda Universitatia Ospedaliera San Giovanni Battista
Torino, 10126
Poland6 sites
Centrum Neurologii Klinicznej
Krakow, 31-530
NZOZ Polimedica
Lodz, 90-302
Wojewódzki Szpital Specjalistyczny w Lublinie Oddzial Neurologii
Lublin, 20-178
Wojewódzki Szpital Specjalistyczny w Olsztynie, Oddzial Neurologii
Olsztyn, 10-561
NZOZ "NEURO - KARD,"Ilkowski I Partnerzy Spólka, Partnerska Lekarzy
Poznan, 61-289
Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna
Warsaw, 02-957
Germany5 sites
Epilepsie-Zentrum Berlin Brandenburg am Evangelischen Krankenhaus Königin Elisabeth Herzberge
Berlin, 10365
Charite, Universitätsmedizin Berlin, CVK
Berlin, 13353
Universitätsklinikum Essen
Essen
Klinik für Neurologie, Klinische Neurophysiologie und Stroke Unit
Munich, 81925
Klinik und Poliklinik für Neurologie der Universität Regensburg im Bezirksklinikum
Regensburg, 93053
Belgium3 sites
Centre Neurologique William Lennox
Ottignies, 1340
Clinique Saint-Pierre
Ottignies, 1340
AZ. Sint-Augustinus
Wilrijk, 2610
Canada3 sites
University of Calgary Clinical Neurosciences
Calgary, Alberta, T2N2T9
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A2B4
BC Children's Hospital
Vancouver, British Columbia, V6H3V4
Greece3 sites
Evangelismos General Hospital
Athens, 10676
Agios Loukas (St. Luke's) Hospital
Thessaloniki, 55236
General Hospital of Thessaloniki "Papanikolaou"
Thessaloniki, 57010
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 Trial
The purpose of this study is to determine whether Eslicarbazepine acetate (BIA 2-093) is an effective adjunct therapy in the treatment of refractory partial seizures
Read the detailed description
The study was designed to include 3 parts; only the first part is described in this report. Part I of the study was an international, randomized, placebo-controlled, double-blind, parallel group, multicenter clinical study conducted in 19 countries at 173 sites in 653 subjects with refractory simple partial or complex partial seizures, with or without secondary generalization. After screening procedures and confirming eligibility, subjects entered Part I of the study, which consisted of 3 periods.
The first period was an 8 week observation baseline period (Week -8 to Week -1) during which subjects were instructed on how to complete the seizure diary. At the end of the 8 week observational baseline period, eligible subjects were randomized in a 1:1:1 allocation ratio to 1 of 3 treatment groups (with a blinded treatment assignment):
- Placebo
- ESL 800 mg QD
- ESL 1200 mg QD Subjects then entered the second period of Part 1, the 2 week, double blind, up titration period (Week 1 to Week 2). During this period, subjects in the ESL 800 mg group received ESL 400 mg QD, subjects in the ESL 1200 mg group received ESL 800 mg QD, and subjects in the placebo group received placebo QD.
Subjects then entered the third period of Part I, the 12 week, double-blind, maintenance period (Week 3 to Week 14) where subjects in the ESL 800 mg group received ESL 800 mg QD, subjects in the ESL 1200 mg group received ESL 1200 mg QD, and subjects in the placebo group received placebo QD.
At the completion of the maintenance period, subjects who did not enter Part II were to be tapered off study drug while maintaining the blind according to the following down titration procedure: subjects on 800 mg were down titrated to 400 mg for a duration of 2 weeks, and subjects on 1200 mg were down titrated to 800 mg for 1 week and then down-titrated to 400 mg for 1 week and subjects in the placebo group received placebo QD for 2 weeks. During Part I, 1 to 2 concomitant AEDs were allowed in this study and were to be kept stable during the course of the study.
- Conditions
- Partial Epilepsy
- Being tested
- 800 mg QD Eslicarbazepine acetate, 1200 mg QD Eslicarbazepine acetate, Placebo
- Keywords
- Refractory, partial, epilepsy, efficacy, eslicarbazepine, safety
- 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.
800 mg QD Eslicarbazepine acetateDrug
Also called BIA 2-093
Oral, 800 mg QD, 2-week titration period and 12-week maintenance period
1200 mg QD Eslicarbazepine acetateDrug
Also called BIA 2-093
Oral, 1200 mg QD, 2-week titration followed by 12-week maintenance period
PlaceboDrug
Also called Sugar pills
Placebo tablet given QD
| Study group | Role | What they receive |
|---|---|---|
| 800 mg QD Eslicarbazepine acetate | Active comparator | tablets Receives: Drug: 800 mg QD Eslicarbazepine acetate |
| 1200 mg QD Eslicarbazepine acetate | Active comparator | tablets Receives: Drug: 1200 mg QD Eslicarbazepine acetate |
| Placebo | Placebo comparator | tablets Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seizure Frequency Over the 12-week Maintenance Period.
Measured: 12-week maintenance period (Week 3 to week 14)
Secondary outcomes (1)
Proportion of Responders
Subjects who had at least a 50% reduction from baseline in standardized seizure frequency during the maintenance period were classified as responders.
Measured: Baseline (Week-8 through Week -1) and Maintenance period (Week 3 to week 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2009 (estimated)
- Study start2 Dec 2008
- Primary completion12 Jan 2012
- Study completion12 Jan 2012
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 (2)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 653 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sumitomo Pharma America, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00988429
- Sponsor's protocol ID
- BIA-2093-304
- Other IDs
- 2008-002455-25, 2008
- Status last verified
- Oct 2018
- First submitted
- 1 Oct 2009
- Last updated
- 19 May 2021
- 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 33338829Cramer JA, Colman S, Anastassopoulos KP, Grinnell T, Mehta D, Williams GR. Associations between seizure severity change and patient characteristics, changes in seizure frequency, and health-related quality of life in patients with focal seizures treated with adjunctive eslicarbazepine acetate: Post hoc analyses of clinical trial results. Epilepsy Behav. 2020 Nov;112:107312. doi: 10.1016/j.yebeh.2020.107312. Epub 2020 Aug 12.
PubMed 32801102