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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT00957047
First received: August 10, 2009
Last updated: June 23, 2014
Last verified: June 2014
  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
Drug: ESL - Part II
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:


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

Primary Outcome Measures:
  • PART I - Seizure Frequency [ Time Frame: 12-week maintenance period ] [ Designated as safety issue: No ]
    The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the 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.

  • PART II - Nº of Treatment-Emergent Adverse Events (TEAE) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Safety assessments were based primarily on AEs (Number of patients who experienced at least one AEs), and on whether these were related to the study medication, were serious, led to permanent discontinuation of study participation, or led to death.


Enrollment: 395
Study Start Date: July 2004
Study Completion Date: January 2008
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ESL 400 mg once daily
Eslicarbazepine acetate (ESL) was supplied in 400 mg tablets for Part I
Drug: eslicarbazepine acetate
oral tablets
Other Name: Zebinix
Experimental: ESL 800 mg once daily
Eslicarbazepine acetate (ESL) was supplied in 800-mg tablets for Part I
Drug: eslicarbazepine acetate
oral tablets
Other Name: Zebinix
Experimental: ESL 1200 mg once daily
Eslicarbazepine acetate (ESL) was supplied in 400-mg and 800-mg tablets for Part I
Drug: eslicarbazepine acetate
oral tablets
Other Name: Zebinix
Placebo Comparator: placebo
Placebo tablets matching the 400-mg and 800-mg active substance tablets were supplied
Drug: placebo
once daily placebo comparator
Other Name: Sugar pill
Experimental: ESL - Part II
All patients in Part II (Open-label Extension ) received ESL on an open-label basis, starting at 800 mg once daily.
Drug: ESL - Part II
Eslicarbazepine acetate was supplied as scored 800-mg tablets for daily oral administration.
Other Name: Eslicarbazepine acetate (ESL), BIA 2-093

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Portugal
Bial - Portela & Cª, S.A.
S. Mamede do Coronado, Portugal, 4745-457
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
Results First Received: March 26, 2013
Last Updated: June 23, 2014
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
Eslicarbazepine acetate
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 18, 2014