Eslicarbazepine Acetate (BIA 2-093) as Monotherapy in Patients With Newly Diagnosed Partial-onset Seizures

NCT ID: NCT02484001

Last Updated: 2018-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-01
• Study Completion Date: 2018-09-11

Brief Summary

This is a Phase III, multinational, open-label, non-controlled study with subjects under treatment in the double-blind BIA-2093-311 study (NCT01162460).

Subjects will enter the open-label extension study after the preceding double-blind study was unblinded and they are attending their last Extension Phase Visit (EPV) of the double-blind study.

For all subjects, the day of the last EPV of the double-blind study will also be the day of Visit 1 for the open-label extension study. All subjects will receive Eslicarbazepine acetate (ESL) under open-label conditions at Visit 1.

The complete study duration including treatment with ESL under open-label conditions and follow-up is expected to last approximately 2 years (105 weeks).

In case ESL as monotherapy will achieve MA prior to the end of 2017, the study may be discontinued prematurely within 42 days after achievement of MA.

Detailed Description

For all subjects participating in this open-label extension study, the last Extension Phase Visit (EPV) of the double-blind study will also be the day of Visit 1 for this study. At this visit, the subjects will be asked if they are willing to continue in an open-label extension and to receive treatment with Eslicarbazepine acetate (ESL) for up to additional 2 years. In case marketing authorization (MA) of ESL as monotherapy will be achieved prior to the end of 2017, the study may be discontinued prematurely within 42 days after achievement of MA.

For subjects not willing to enter the extension study, IMP from the double-blind study (CBZ-CR or ESL) is to be discontinued according to the down-titration scheme in the clinical study protocol and commercially available antiepileptic drug (AED) is to be introduced according to investigator's discretion.

In case the subject is willing to enter the extension study, subjects already treated with ESL will continue with their last evaluated dose (ESL 800 mg, 1200 mg or 1600 mg QD).

Subjects previously treated with CBZ-CR will start with ESL 400 mg QD for one week followed by up-titration to the ESL target dose which is equivalent to the last evaluated CBZ-CR dose level (i.e. CBZ-CR 200 mg BID -> ESL 800 mg QD; CBZ-CR 400 mg BID -> ESL 1200 mg QD; CBZ-CR 600 mg BID -> ESL 1600 mg QD) in steps of 400 mg dose increase per week.

All subjects previously treated with CBZ-CR, regardless of their last evaluated dose level, will start CBZ-CR down-titration two weeks after first receipt of ESL treatment as part of the double-blind study and as outlined in the BIA-2093-311 study protocol.

In case of new seizures, the ESL dose can be increased to a maximum dose of ESL 1600 mg QD [dose level C], depending on the investigator's decision. Any up-titration should be performed in weekly steps of 400 mg.

If according to the investigator's opinion the subject may benefit from a combination treatment, an additional commercially available AED as add-on can be introduced at the investigator's discretion.

If deemed necessary by the investigator, e.g. due to occurrence of adverse events, the dose of ESL can be reduced according to investigator's discretion, as long as the dose remains in the range of 800 mg QD to 1600mg QD.

In case the subject started with the extension study but is not willing to continue at any time, the subject has to be switched to commercially available AEDs to receive the best standard of care according to the investigator's discretion. Down-titration of ESL as required should be performed in steps of 400 mg decrease per week

Conditions

Epilepsy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ESL 800 mg

ESL will be administered orally once daily (QD)

Group Type: EXPERIMENTAL

ESL 800 mg

Intervention Type: DRUG

one (1) tablet of 800 mg (QD).

ESL 1200 mg

ESL will be administered orally once daily (QD)

Group Type: EXPERIMENTAL

ESL 1200 mg

Intervention Type: DRUG

one (1) and a half tablets of 800 mg (QD). ESL tablets are scored and can be divided in two equal halves (each one containing 400 mg ESL)

ESL 1600 mg

ESL will be administered orally once daily (QD)

Group Type: EXPERIMENTAL

ESL 1600 mg

Intervention Type: DRUG

two (2) tablets of 800 mg (QD).

ESL 400 mg

ESL will be administered orally once daily (QD)

Group Type: EXPERIMENTAL

ESL 400 mg

Intervention Type: DRUG

half tablet of 800 mg (QD). ESL tablets are scored and can be divided in two equal halves (each one containing 400 mg ESL)

Interventions

ESL 800 mg

one (1) tablet of 800 mg (QD).

Intervention Type: DRUG

ESL 1200 mg

one (1) and a half tablets of 800 mg (QD). ESL tablets are scored and can be divided in two equal halves (each one containing 400 mg ESL)

Intervention Type: DRUG

ESL 1600 mg

two (2) tablets of 800 mg (QD).

Intervention Type: DRUG

ESL 400 mg

half tablet of 800 mg (QD). ESL tablets are scored and can be divided in two equal halves (each one containing 400 mg ESL)

Intervention Type: DRUG

Other Intervention Names

BIA 2-093; BIA 2-093; BIA 2-093; BIA 2-093

Eligibility Criteria

Inclusion Criteria

For inclusion in the extension study, subjects must fulfill all of the following at Visit 1 (Day 1, start of the open-label extension study):

1. Participated in the preceding double-blind study and were still ongoing at the time of unblinding.

2. Have signed informed consent before undergoing any activities related to the open-label extension study.

3. Demonstrated cooperation and willingness to complete all aspects of the study.

4. Female subjects without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative serum ß-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the Post-study Visit (PSV).

Exclusion Criteria

Subjects having any of the following at Visit 1 are to be excluded from the study:

1. Excluded from the double-blind study due to seizure in the Maintenance or Extension Phase, or at dose level C (either CBZ-CR or ESL), or discontinued prematurely due to any other reason in the double-blind study.

2. Presence of any major protocol violation during the double-blind study which may have an impact on the compliance during this extension study.

3. Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (C-SSRS).

4. Occurrence of an adverse event (AE) indicating a suspected presence of atrioventricular block (2nd degree and above) or of any other AEs during the double-blind study which are judged by the investigator as contraindicative to further participation in the open-label extension study.

5. Events of alcohol, drug, or medication abuse during the preceding double-blind study.

6. Relevant clinical laboratory abnormalities (e.g. sodium <125 mmol/L, alanine or aspartate transaminases >2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (as reported at Visit 1).

7. Pregnancy or lactating.

8. Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject's ability to comply with the extension-study protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bial - Portela C S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Trinka E, Rocamora R, Chaves J, Koepp MJ, Ruegg S, Holtkamp M, Moreira J, Fonseca MM, Castilla-Fernandez G, Ikedo F. Lipid profile with eslicarbazepine acetate and carbamazepine monotherapy in adult patients with newly diagnosed focal seizures: post hoc analysis of a phase III trial and open-label extension study. Ther Adv Neurol Disord. 2023 Sep 4;16:17562864231193530. doi: 10.1177/17562864231193530. eCollection 2023.

Reference Type: DERIVED

PMID: 37675038 (View on PubMed)

Other Identifiers

BIA-2093-311/EXT

Identifier Type: -

Identifier Source: org_study_id