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

NCT00957684 | Completed Phase 3 Results

• 1 other identifier: BIA-2093-301
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Refractory Partial Epilepsy

Keywords

refractory; partial; epilepsy

Outcome Measures

Primary Outcomes (1)

• Part I: Seizure Frequency

  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

  12-week maintenance period

Study Arms (5)

ESL 400 mg once daily

EXPERIMENTAL

ESL was supplied in 400-mg and 800-mg tablets

Drug: eslicarbazepine acetate

ESL 800 mg once daily

EXPERIMENTAL

ESL was supplied in 400-mg and 800-mg tablets

Drug: eslicarbazepine acetate

ESL 1200 mg once daily

EXPERIMENTAL

ESL was supplied in 400-mg and 800-mg tablets

Drug: eslicarbazepine acetate

placebo

PLACEBO COMPARATOR

Placebo matching tablets

Drug: placebo

ESL - PART II

EXPERIMENTAL

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.

Drug: eslicarbazepine acetate

Interventions

eslicarbazepine acetate DRUG

once-daily oral tablet

Also known as: Zebinix

ESL - PART II; ESL 1200 mg once daily; ESL 400 mg once daily; ESL 800 mg once daily

placebo DRUG

once daily placebo comparator

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Bial - Portela & Cª, S.A.

São Mamede do Coronado, 4745-457, Portugal

Location

Related Publications (1)

• 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.

  PMID: 33338829 DERIVED

MeSH Terms

Conditions

Epilepsies, Partial; Epilepsy

Interventions

eslicarbazepine acetate

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Head of Clinical Research Section
• Organization: BIAL - Portela & Ca, SA

clinical.trials@bial.com

351 22 986 6100

Study Officials

• Prof. Christian Elger

  Department of Epileptology, Friedrich Wilhelms University Bonn

  PRINCIPAL INVESTIGATOR

• Prof. Peter Halasz

  National Institute of Psychiatry and Neurology, Budapest, Hungary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2009
• First Posted: August 12, 2009
• Study Start: July 1, 2004
• Primary Completion: November 1, 2005
• Study Completion: February 1, 2007
• Last Updated: March 12, 2025
• Results First Posted: October 10, 2013

Record last verified: 2025-03

Locations

PT (1)