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

Primary Purpose

Partial Epilepsy

Status

Completed

Phase

Phase 3

Locations

Portugal

Study Type

Interventional

Intervention

eslicarbazepine acetate

placebo (Part I)

ESL - Open-label Extension (Part II)

About this trial

This is an interventional treatment trial for Partial Epilepsy focused on measuring 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 Type

Experimental

Placebo Comparator

Experimental

Arm Label

ESL 800 mg daily (Part I)

ESL 1200 mg daily (Part I)

placebo (Part I)

ESL - Open-label Extension (Part II)

Arm Description

ESL 800mg daily

ESL 1200mg daily

placebo

All patients were treated with only ESL during Part II.

Outcomes

Primary Outcome Measures

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 results for the ITT population during the 12-week maintenance period. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate

PART II: Nº of Treatment-Emergent Adverse Events (TEAE)

The primary objective for Part II of the study was to evaluate the safety and tolerability of eslicarbazepine acetate (ESL, BIA 2-093) at doses titrated to an efficacy or safety endpoint over a 1-year open-label period. Safety assessments were based primarily on AEs (Number of participants with at least one treatment-emergent adverse events are reported); assessment of AEs was based on treatment relatedness, action taken on study drug, outcome, and causality.

Secondary Outcome Measures

Full Information

NCT ID

NCT00957372

First Posted

August 10, 2009

Last Updated

June 23, 2014

Sponsor

Bial - Portela C S.A.

1. Study Identification

Unique Protocol Identification Number

NCT00957372

Brief Title

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

Official Title

Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

June 2014

Overall Recruitment Status

Completed

Study Start Date

December 2004 (undefined)

Primary Completion Date

June 2008 (Actual)

Study Completion Date

June 2008 (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

The primary objective was to evaluate the efficacy of eslicarbazepine acetate (ESL) administered once daily at 1200 mg or 800 mg, compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period.

Detailed Description

This was a phase III, 2-part multicenter study. Part I was an 26-week parallel-group, randomized, placebo-controlled design consisting of an 8 week baseline period, a 2 week double-blinded titration period, 12 week maintenance period, and a 4 week tapering-off period. After completing the baseline period, patients were randomized in a 1:1:1 ratio to 1 of the 2 ESL daily dose levels (1200 or 800 mg) or placebo. Part II was a 1-year open-label extension for patients who had completed Part I. Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day. Patients who completed Part II could participate in a study extension and continue treatment with ESL until marketing authorization is obtained or clinical development is discontinued, with visits scheduled at the discretion of the investigator but at least every 6 months. Results from Part I & II were presented in two separate reports.

6. Conditions and Keywords

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

Partial Epilepsy

Keywords

epilepsy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

253 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ESL 800 mg daily (Part I)

Arm Type

Experimental

Arm Description

ESL 800mg daily

Arm Title

ESL 1200 mg daily (Part I)

Arm Type

Experimental

Arm Description

ESL 1200mg daily

Arm Title

placebo (Part I)

Arm Type

Placebo Comparator

Arm Description

placebo

Arm Title

ESL - Open-label Extension (Part II)

Arm Type

Experimental

Arm Description

All patients were treated with only ESL during Part II.

Intervention Type

Drug

Intervention Name(s)

eslicarbazepine acetate

Other Intervention Name(s)

Zebinix

Intervention Description

oral tablet, 800 mg or 1200 mg once daily

Intervention Type

Drug

Intervention Name(s)

placebo (Part I)

Intervention Description

once daily placebo comparator

Intervention Type

Drug

Intervention Name(s)

ESL - Open-label Extension (Part II)

Intervention Description

Part II was a 1-year open-label extension for patients who had completed Part I. Starting at 800 mg/day, the dosage could be titrated at 400 mg intervals down to a minimum of 400 mg/day or up to a maximum of 1200 mg/day

Primary Outcome Measure Information:

Title

Seizure Frequency

Description

Time Frame

12 weeks

Title

PART II: Nº of Treatment-Emergent Adverse Events (TEAE)

Description

Time Frame

1-year

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

Antonio Gil-Nagel, MD

Organizational Affiliation

Hospital Ruber Internacional La Masó 38, Mirasierra 28034 Madrid, Spain

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jose Lopes-Lima, MD

Organizational Affiliation

Hospital Santo António Largo Prof. Abel Salazar, 4099-001 Porto, Portugal

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

Learn more about this trial

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

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