Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy - Full Text View

Purpose

The primary objective of the study is to evaluate the efficacy of eslicarbazepine acetate once-daily at doses of 400 mg, 800 mg and 1200 mg compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period. Patients who complete Part I may enter a 1-year open-label extension.

Condition	Intervention	Phase
Partial Epilepsy	Drug: eslicarbazepine acetate Drug: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial

Resource links provided by NLM:

Genetics Home Reference related topics: autosomal dominant partial epilepsy with auditory features pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy Seizures

U.S. FDA Resources

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

Primary Outcome Measures:

seizure frequency standardized to 'frequency per 4 weeks' [ Time Frame: 12-week maintenance period ] [ Designated as safety issue: No ]
The primary efficacy endpoint was seizure frequency over the 12-week maintenance period in Part I of the study, standardized to a "frequency per 4 weeks" unit.

Secondary Outcome Measures:

proportion of responders [ Time Frame: 12-week maintenance ] [ Designated as safety issue: No ]
patients with a ≥ 50% reduction in seizure frequency during the 12-week maintenance period compared with the 8-week baseline period
seizure frequency per week for each week of the baseline, titration, and maintenance periods [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
distribution of seizure reduction (< 50%, 50-75%, or > 75% seizure reduction) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
proportion of seizure-free patients (100% seizure reduction) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
proportion of patients with a ≥ 25% exacerbation in seizure frequency compared to baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
seizure frequency by seizure type [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Number of AES/patient

Enrollment:	395
Study Start Date:	July 2004
Study Completion Date:	December 2006
Primary Completion Date:	August 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ESL 400 mg once daily	Drug: eslicarbazepine acetate oral tablets Other Name: Zebinix
Experimental: ESL 800 mg once daily	Drug: eslicarbazepine acetate oral tablets Other Name: Zebinix
Experimental: ESL 1200 mg once daily	Drug: eslicarbazepine acetate oral tablets Other Name: Zebinix
Placebo Comparator: placebo	Drug: placebo once daily placebo comparator

Detailed Description:

Part I was a 22-week parallel-group, randomized, placebo-controlled period (8 weeks baseline, 2 weeks double-blind titration, and 12 weeks maintenance). After completing the baseline period, patients were randomized in a 1:1:1:1 ratio to 1 of the 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957047

Locations

Brazil
Rua Pedro de Toledo 655
Sao Paulo, Vila Clementino, Brazil, 04039-302
Sweden
Sahlgrenska University Hospital
Göteborg, Sweden, 41345

Sponsors and Collaborators

Bial - Portela C S.A.

Investigators

Principal Investigator:	Elinor Ben-Menachem, MD	Sahlgren University Hospital, Göteborg, Sweden
Principal Investigator:	Alberto Alain Gabbai, MD	Rua Pedro de Toledo 655, Vila Clemento, Sao Paulo, Brazil

More Information

No publications provided

Responsible Party:	Bial - Portela C S.A.
ClinicalTrials.gov Identifier:	NCT00957047 History of Changes
Other Study ID Numbers:	BIA-2093-302
Study First Received:	August 10, 2009
Last Updated:	June 18, 2012
Health Authority:	Portugal: National Pharmacy and Medicines Institute

Keywords provided by Bial - Portela C S.A.:

refractory
partial
epilepsy

Additional relevant MeSH terms:

Epilepsy
Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013