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

Primary Purpose

Refractory Partial Epilepsy

Status

Completed

Phase

Phase 3

Locations

Portugal

Study Type

Interventional

Intervention

eslicarbazepine acetate

placebo

About this trial

This is an interventional treatment trial for Refractory Partial Epilepsy focused on measuring refractory, partial, epilepsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Bial - Portela & Cª, S.A.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

ESL 400 mg once daily

ESL 800 mg once daily

ESL 1200 mg once daily

placebo

ESL - PART II

Arm Description

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

Placebo matching tablets

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT00957684

First Posted

August 10, 2009

Last Updated

June 23, 2014

Sponsor

Bial - Portela C S.A.

1. Study Identification

Unique Protocol Identification Number

NCT00957684

Brief Title

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

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 Clinical Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2014

Overall Recruitment Status

Completed

Study Start Date

July 2004 (undefined)

Primary Completion Date

November 2005 (Actual)

Study Completion Date

February 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bial - Portela C S.A.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Refractory Partial Epilepsy

Keywords

refractory, partial, epilepsy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

402 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ESL 400 mg once daily

Arm Type

Experimental

Arm Description

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

Arm Title

ESL 800 mg once daily

Arm Type

Experimental

Arm Description

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

Arm Title

ESL 1200 mg once daily

Arm Type

Experimental

Arm Description

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

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Placebo matching tablets

Arm Title

ESL - PART II

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

eslicarbazepine acetate

Other Intervention Name(s)

Zebinix

Intervention Description

once-daily oral tablet

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

once daily placebo comparator

Primary Outcome Measure Information:

Title

Part I: Seizure Frequency

Description

Time Frame

12-week maintenance period

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Prof. Christian Elger

Organizational Affiliation

Department of Epileptology, Friedrich Wilhelms University Bonn

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Prof. Peter Halasz

Organizational Affiliation

National Institute of Psychiatry and Neurology, Budapest, Hungary

Official's Role

Principal Investigator

Facility Information:

Facility Name

Bial - Portela & Cª, S.A.

City

S. Mamede do Coronado

ZIP/Postal Code

4745-457

Country

Portugal

12. IPD Sharing Statement

Citations:

PubMed Identifier

33338829

Citation

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.

Results Reference

derived

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

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