Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures

Partial Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00988429
• Other study ID #: BIA-2093-304
• Secondary ID: 2008-002455-25
• Status: Completed
• Phase: Phase 3
• Start date: December 2, 2008
• Est. completion date: January 12, 2012

Study information

• Verified date: October 2018
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 653
• Est. completion date: January 12, 2012
• Est. primary completion date: January 12, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria

At V1 (screening), patient must be/have:

1. Written informed consent signed by patient.

2. 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.

3. A documented diagnosis of epilepsy since at least 12 months prior to screening.

4. 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.

5. 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).

6. Excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination findings, and clinical laboratory test results.

7. 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:

8. 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.

9. In case of WOCBP, patient must present a urine B-hCG test consistent with a non gravid state.

10. Diaries satisfactorily completed by the patient or his/her caregiver.

11. Satisfactorily complied with the study requirements during the baseline period (including no changes in concomitant AED therapy should have occurred in the baseline period).

Exclusion Criteria

At V1 (screening), patients must not be/have:

1. Only simple partial seizures with no motor symptomatology (classified as A2 4 according to the International Classification of Epileptic Seizures).

2. Primarily generalised seizures.

3. Known progressive neurological disorders (progressive brain disease; epilepsy secondary to progressive cerebral lesion).

4. Occurrence of seizures too close to count accurately.

5. History of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months prior to screening.

6. Seizures of non-epileptic origin.

7. Seizures of psychogenic origin within the last 2 years.

8. Major psychiatric disorders.

9. 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.

10. Currently treated with OXC.

11. Using benzodiazepines on more than an occasional basis (defined as more than 2 times per week), except when used chronically as AED.

12. 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).

13. Known hypersensitivity to carboxamide derivatives.

14. History of abuse of alcohol, drugs or medications within the last 2 years.

15. Uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder.

16. Second or third-degree atrioventricular blockade not corrected with a pacemaker.

17. 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.

18. 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].

19. Pregnant or nursing.

20. 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.

21. Not ensured capability to perform the trial.

22. Any other condition or circumstance that, in the opinion of the Investigator, may compromise the patient's ability to comply with the study protocol.

23. 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:

24. Inadequate compliance to concomitant AEDs during the 8-week baseline period or to screening exclusion criteria.

25. Inadequate completion of the study diary.

26. Any other condition or circumstance that, in the opinion of the Investigator, may compromise the patient's ability to comply with the study protocol.

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Partial Epilepsy
• Seizures

Intervention

Drug:
• 800 mg QD Eslicarbazepine acetate
Oral, 800 mg QD, 2-week titration period and 12-week maintenance period
• 1200 mg QD Eslicarbazepine acetate
Oral, 1200 mg QD, 2-week titration followed by 12-week maintenance period
• Placebo
Placebo tablet given QD

Locations

Country	Name	City	State
Argentina	CEMIC	Buenos Aires
Argentina	Centro Neurológico de Tratamiento y Rehabilitación	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Privado de la comunidad de Mar de Plata	Buenos Aires
Argentina	Fleni	Capital Federal
Argentina	Hospital Británico	Capital Federal
Argentina	Hospital Ramos Mejía	Capital Federal
Argentina	Instituto Médico Especializado (IME)	Capital Federal
Argentina	Centro de Neurologia y Neurorehabilitacion	Cordoba
Argentina	Hospital Privado - Centro Médico de Córdoba S.A.	Cordoba
Belgium	Centre Neurologique William Lennox	Ottignies
Belgium	Clinique Saint-Pierre	Ottignies
Belgium	AZ. Sint-Augustinus	Wilrijk
Brazil	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte
Brazil	Hospital das Clínicas - UNICAMP	Campinas
Brazil	Instituto de Neurologia de Curitiba	Curitiba
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre
Brazil	Hospital São Lucas - PUCRS	Porto Alegre
Brazil	Hospital das Clinicas da FMRP	Ribeirão Preto
Brazil	Faculdade de Medicina do ABC	Santo André
Brazil	Hospital São Paulo - UNIFESP	Sao Paulo
Brazil	Hospital Brigadeiro	São Paulo
Brazil	Irmandade da Santa Casa de Misericórdia de São Paulo	São Paulo
Canada	University of Calgary Clinical Neurosciences	Calgary	Alberta
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	BC Children's Hospital	Vancouver	British Columbia
Cyprus	The Cyprus Institute of Neurology	Nikosia
France	CENTRE HOSPITALIER PELLEGRIN, CHU de BORDEAUX	Bordeaux
France	Hopital Femme-Mere-Enfant, Hospices Civils de Lyon	Bron
France	Hopital Roger Salengro, Chru de Lille	Lille
France	Hopital Gui de Chauliac, Chu de Montpellier	Montpellier
France	Hopital Central, Chu de Nancy	Nancy
France	Centre Hospitalier Sainte-Anne	Paris
France	Hopital Pontchaillou, Chru de Rennes	Rennes
France	Hopital Civil, Chru de Strasbourg	Strasbourg
Germany	Charite, Universitätsmedizin Berlin, CVK	Berlin
Germany	Epilepsie-Zentrum Berlin Brandenburg am Evangelischen Krankenhaus Königin Elisabeth Herzberge	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Klinik für Neurologie, Klinische Neurophysiologie und Stroke Unit	Munich
Germany	Klinik und Poliklinik für Neurologie der Universität Regensburg im Bezirksklinikum	Regensburg
Greece	Evangelismos General Hospital	Athens
Greece	Agios Loukas (St. Luke's) Hospital	Thessaloniki
Greece	General Hospital of Thessaloniki "Papanikolaou"	Thessaloniki
Italy	Azienda Ospedaliero, Universitaria "Ospedali Riuniti", Clinica della Malattie del Sistema Nervoso, Università di Foggia	Foggia
Italy	A.O.U Policlinico di Messina	Messina
Italy	Università degli Studi di Napoli Policlinico Federico II	Napoli
Italy	Azienda Ospedaliero - Universitaria Maggiore della Carità	Novara
Italy	Istituto Neurologico Casimiro Mondino	Pavia
Italy	Università Cattolica del Sacro Cuore Policlinico "A. Gemelli"	Roma
Italy	Azienda Universitatia Ospedaliera San Giovanni Battista	Torino
Poland	Centrum Neurologii Klinicznej	Kraków
Poland	NZOZ Polimedica	Lodz
Poland	Wojewódzki Szpital Specjalistyczny w Lublinie Oddzial Neurologii	Lublin
Poland	Wojewódzki Szpital Specjalistyczny w Olsztynie, Oddzial Neurologii	Olsztyn
Poland	NZOZ "NEURO - KARD,"Ilkowski I Partnerzy Spólka, Partnerska Lekarzy	Poznan
Poland	Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna	Warszawa
United States	Albany Medical College - Neurosciences Institute	Albany	New York
United States	McFarland Clinic, PC	Ames	Iowa
United States	University of Colorado Health Sciences	Aurora	Colorado
United States	Kern County Neurological Medical Group, INC.	Bakersfield	California
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Neurological Associates of Washington/Clinical Trials of America, Inc	Bellevue	Washington
United States	Mid-Atlantic Epilepsy and Sleep Centre	Bethesda	Maryland
United States	Consultants in Epilepsy and Neurology, PPLC	Boise	Idaho
United States	MGH Epilepsy Service Massachusetts, General Hospital	Boston	Massachusetts
United States	Bradenton Research Center	Bradenton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Private Practice of Dr. Edwin Green	Brownwood	Texas
United States	The Cooper Health System	Camden	New Jersey
United States	Five Towns Neuroscience Research	Cedarhurst	New York
United States	The Neurological Institute, P.A.	Charlotte	North Carolina
United States	University of Virginia - Comprehensive Epilepsy Program	Charlottesville	Virginia
United States	The Comprehensive Epilepsy Care Centre for Chidren and Adults	Chesterfield	Missouri
United States	Ohio State University Medical Centre	Columbus	Ohio
United States	Arkansas Neurology	Conway	Arkansas
United States	Neurological Clinic of Texas	Dallas	Texas
United States	Neurology Consultants of Dallas, P.A.	Dallas	Texas
United States	Texas Neurology, PA	Dallas	Texas
United States	UTSWMC Department of Neurology, Division of Epilepsy Research	Dallas	Texas
United States	Neurology Specialists, Inc	Dayton	Ohio
United States	Denver Health	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Medistat Clinical Research	DeSoto	Texas
United States	Nemmar Clinical Resources	DeSoto	Texas
United States	Wayne State University/Detroit Medical Center	Detroit	Michigan
United States	Precise Research Centers	Flowood	Mississippi
United States	Neuro-Pain Medical Center, Inc.	Fresno	California
United States	Optima Neurological Services, LLC	Gainesville	Florida
United States	University of Florida Department of Neurology	Gainesville	Florida
United States	Clinical Research Centre of New Jersey	Gibbsboro	New Jersey
United States	Minneapolis Clinic of Neurology, Ltd	Golden Valley	Minnesota
United States	NW FL Clinical Research Group, LLC	Gulf Breeze	Florida
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	Palm Springs Research Institute	Hialeah	Florida
United States	PMG Research of Hickory, LLC	Hickory	North Carolina
United States	Houston Neurology and Sleep Center	Houston	Texas
United States	Josephson Wallack Munshower Neurology P.C.	Indianapolis	Indiana
United States	University of Florida	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Clinical Trials Inc.	Little Rock	Arkansas
United States	Neurological Care of CNY	Liverpool	New York
United States	Loma Linda University	Loma Linda	California
United States	Collaborative Neuroscience Network, INC	Long Beach	California
United States	Dean & St. Mary's Outpatient Center Neurological Institute and Spine Center	Madison	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Kendall South Medical Center, Inc.	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	Neuroscience Consultants	Miami	Florida
United States	Pharmax Research Clinic	Miami	Florida
United States	University of Miami - Miller School of Medicine Department of Neurology	Miami	Florida
United States	Medical College of Wisconsin - Department of Neurology	Milwaukee	Wisconsin
United States	Regional Epilepsy Centre of Aurora Healthcare- St. Luke's Medical Centre	Milwaukee	Wisconsin
United States	University of South Alabama Department of Neurology	Mobile	Alabama
United States	Viking Clinical Research Center	Murrieta	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	UMDNJ-Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Louisiana Research Associates, Inc.	New Orleans	Louisiana
United States	LSUHSC Epilepsy Center	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	NYU Comprehensive Epilepsy Centre	New York	New York
United States	Wiell Cornell Medical Centre Epilepsy Centre	New York	New York
United States	Sentara Medical Group, Neurology Specialists Sentara Heart Hospital	Norfolk	Virginia
United States	Neurology Clinic, P.C.	Northport	Alabama
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Dent Neurologic Institute	Orchard Park	New York
United States	St. Joseph Regional Medical Center	Paterson	New Jersey
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Comprehensive Epilepsy Center - Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Temple University School of Medicine - Department of Neurology	Philadelphia	Pennsylvania
United States	21st Century Neurology - Division of Xenoscience, Inc.	Phoenix	Arizona
United States	Barrow Neurological Institute / St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Phoenix Neurological Associates/Clinical Research Advantage	Phoenix	Arizona
United States	Childrens Hospital of Pittsburg of UPMC - Division of Child Neurology	Pittsburgh	Pennsylvania
United States	Medsol Clinical Research Center	Port Charlotte	Florida
United States	Ranier Clinical Research Center	Renton	Washington
United States	Strong Epilepsy Center - University of Rochester Medical Center	Rochester	New York
United States	Harbin Clinic	Rome	Georgia
United States	Minnesota Epilepsy Group, P.A.	Saint Paul	Minnesota
United States	Wasatch Clinical Research	Salt Lake City	Utah
United States	Innovative Clinical Trials	San Antonio	Texas
United States	Road Runner Research	San Antonio	Texas
United States	Bright Minds Institute	San Francisco	California
United States	Milestone Clinical Research	San Jose	California
United States	Lovelace Scientific Resources	Sarasota	Florida
United States	University Washington Regional Epilepsy Center Harborview	Seattle	Washington
United States	Southern Ilinois University School of Medicine	Springfield	Illinois
United States	ANI Research, PC	Sun City	Arizona
United States	SUNY Upstate Medical University	Syracuse	New York
United States	MultiCare Adult Neurology	Tacoma	Washington
United States	Pediatric Epilepsy & Neurology Specialists, PA	Tampa	Florida
United States	University of South Florida - Department of Neurology	Tampa	Florida
United States	Scott and White Memorial Hospital Sherwood and Brindley Foundation	Temple	Texas
United States	University of Toledo - Health Science Campus	Toledo	Ohio
United States	Shore Neurology, PA	Toms River	New Jersey
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	Tulsa Clinical Reserch	Tulsa	Oklahoma
United States	Lovelace Scientific Resources	Venice	Florida
United States	Neurosearch II, Inc.	Ventura	California
United States	Palm Beach Clinical Research Network, LLC.	Wellington	Florida
United States	Wilmington Medical Research	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Bial - Portela C S.A.	Sunovion

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Cyprus,  France,  Germany,  Greece,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizure Frequency Over the 12-week Maintenance Period.		12-week maintenance period (Week 3 to week 14)
Secondary	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.	Baseline (Week-8 through Week -1) and Maintenance period (Week 3 to week 14)