Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT00957684
First received: August 10, 2009
Last updated: June 23, 2014
Last verified: June 2014

August 10, 2009
June 23, 2014
July 2004
November 2005   (final data collection date for primary outcome measure)
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 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
Seizure frequency [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00957684 on ClinicalTrials.gov Archive Site
Not Provided
  • Proportion of patients with a 50% or greater reduction in seizure frequency [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Adverse events, clinical laboratory tests (haematology, coagulation, biochemistry, thyroid function, and urinalysis), vital signs and weight, electrocardiogram (ECG), blood trough levels of concomitant AEDs, withdrawal and/or rebound effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures
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.

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).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Refractory Partial Epilepsy
  • Drug: eslicarbazepine acetate
    once-daily oral tablet
    Other Name: Zebinix
  • Drug: placebo
    once daily placebo comparator
  • Experimental: ESL 400 mg once daily
    ESL was supplied in 400-mg and 800-mg tablets
    Intervention: Drug: eslicarbazepine acetate
  • Experimental: ESL 800 mg once daily
    ESL was supplied in 400-mg and 800-mg tablets
    Intervention: Drug: eslicarbazepine acetate
  • Experimental: ESL 1200 mg once daily
    ESL was supplied in 400-mg and 800-mg tablets
    Intervention: Drug: eslicarbazepine acetate
  • Placebo Comparator: placebo
    Placebo matching tablets
    Intervention: Drug: placebo
  • Experimental: ESL - PART II
    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.
    Intervention: Drug: eslicarbazepine acetate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
402
February 2007
November 2005   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Portugal
 
NCT00957684
BIA-2093-301
No
Bial - Portela C S.A.
Bial - Portela C S.A.
Not Provided
Principal Investigator: Prof. Christian Elger Department of Epileptology, Friedrich Wilhelms University Bonn
Principal Investigator: Prof. Peter Halasz National Institute of Psychiatry and Neurology, Budapest, Hungary
Bial - Portela C S.A.
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP