Epilepsy
Conditions
Keywords
Epilepsy, ESL, Eslicarbazepine Acetate, BIAL, BIA, Partial-onset Seizures
Brief summary
This is an open Label study to investigate the safety and efficacy of eslicarbazepine acetate as adjunctive therapy for partial seizures in elderly patients.
Detailed description
Multicenter study in approximately 100 elderly patients. The study will follow an open-label design and will consist of 8-week baseline period, followed by a 26-week treatment period and a 4-week follow-up period.
Interventions
ESL tablets (800 mg) QD
Sponsors
Bial - Portela C S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent form; 2. Of age 65 years or older; 3. A documented diagnosis of epilepsy for at least 12 months, 4. At least 2 partial-onset seizures (including subtypes of simple partial, complex partial and/or partial seizures evolving to secondarily generalised) in the 4 weeks prior to screening; 5. Currently treated with 1 or 2 AEDs (any except oxcarbazepine) in a stable dosage regimen for at least 4 weeks prior to screening. Vagus nerve stimulation (VNS) is to be considered as an AED (i.e., only one concomitant AED is allowed in patients with VNS); 6. Willing and able to comply with all trial requirements, in the judgment of the investigator; 7. At least 2 partial-onset seizures (documented in the diary) per 4 weeks during the 8-week baseline period; 8. Satisfactorily complied with the study requirements during the baseline period
Exclusion criteria
1. Only simple partial seizures with no motor symptomatology (classified as A2-4) according to the International Classification of Epileptic Seizures); 2. Primarily generalised seizures; 3. Known progressive neurological disorders (progressive brain disease, epilepsy secondary to progressive central nervous system lesion) and progressive dementia; 4. Occurrence of seizures too close to count accurately; 5. History of status epileptic or cluster seizures 8i.e. 3 or more seizures within 30 minutes) within the 3 months prior to screening; 6. Seizures of non-epileptic origin; 7. Major psychiatric disorders; 8. History of suicide attempt; 9. Currently treated with oxcarbazepine; 10. Previous use of ESL or participation in a clinical study with ESL; 11. Known hypersensitivity to other carboxamide derivatives (e.g. oxcarbazepine, carbamazepine) or to any of the excipients; 12. Uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder, hypo - or hyper thyroidism of any type; 13. Second or third-degree atrioventricular blockade or any clinically significant abnormality in the 12-lead electrocardiogram (ECG) as determined by the investigator; 14. Relevant clinical laboratory abnormalities as determined by the investigator (e.g. plasma sodium \<130 mmol/L, alanine or aspartate aminotransferases \>2.0 times above the upper limit of the range, or white blood cell count \<3,000 cells/mm3; 15. Calculated creatinine values \< 30 mL/min at screening; 16. Any other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol; 17. Received an investigational drug (or a medical device) within 3 months of screening or is currently participating in another trial of an investigational drug (or medical device) trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Reported Adverse Events (AE) | throughout the study | An AE was defined as Treatment-Emergent Adverse Event (TEAE), if first onset or worsening was after the first intake of investigational medicinal product (IMP) and not more than 14 days after the last administration of IMP. TEAE assessment: * patients who died * patients who died due to Treatment-emergent adverse event (TEAE) * patients with at least one Serious Adverse Event (SAE) * patients with at least one Treatment-emergent Serious Adverse Event (TESAE) * patients prematurely terminated due to TEAE * patients with at least one TEAE * patients with at least one related TEAE * patients with at least one severe TEAE * patients without any TEAE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Standardized Seizure Frequency | 8-week Baseline Period and 26-week Treatment Period | Absolute and relative changes from baseline of seizure frequency standardised to a frequency per 4 weeks. |
Countries
Austria, Bulgaria, Croatia, Czechia, France, Germany, Poland, Portugal, Romania, Spain
Participant flow
Recruitment details
44 clinical centres in Europe and Asia. Studied period (years): Date of first enrolment: 19-APR-2010 Date of last subject completed: 08-OCT-2013
Pre-assignment details
In this trial all subjects received the same treatment.
Participants by arm
| Arm | Count |
|---|---|
| Esl 800 mg Eslicarbazepine Acetate (Esl) tablets (800 mg) QD | 72 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | Ineligibility | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Esl 800 mg |
|---|---|
| Age, Customized 65-69 years | 30 participants |
| Age, Customized 70-74 years | 19 participants |
| Age, Customized 75-79 years | 19 participants |
| Age, Customized 80-84 years | 4 participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 43 / 72 |
| serious Total, serious adverse events | 11 / 72 |
Outcome results
Primary
Number of Subjects With Reported Adverse Events (AE)
An AE was defined as Treatment-Emergent Adverse Event (TEAE), if first onset or worsening was after the first intake of investigational medicinal product (IMP) and not more than 14 days after the last administration of IMP. TEAE assessment: * patients who died * patients who died due to Treatment-emergent adverse event (TEAE) * patients with at least one Serious Adverse Event (SAE) * patients with at least one Treatment-emergent Serious Adverse Event (TESAE) * patients prematurely terminated due to TEAE * patients with at least one TEAE * patients with at least one related TEAE * patients with at least one severe TEAE * patients without any TEAE
Time frame: throughout the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients who died | 3 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients who died due to TEAE | 3 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients with at least one SAE | 11 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients with at least one TESAE | 10 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients prematurely terminated due to TEAE | 18 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients with at least one TEAE | 47 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients with at least one related TEAE | 31 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients without any TEAE | 25 participants |
| Esl 800 mg | Number of Subjects With Reported Adverse Events (AE) | patients with at least one severe TEAE | 12 participants |
Secondary
Change From Baseline in Standardized Seizure Frequency
Absolute and relative changes from baseline of seizure frequency standardised to a frequency per 4 weeks.
Time frame: 8-week Baseline Period and 26-week Treatment Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esl 800 mg | Change From Baseline in Standardized Seizure Frequency | 4.8 seizures/4 weeks | Standard Deviation 5.53 |
| FAS - Treatment Period | Change From Baseline in Standardized Seizure Frequency | 3.6 seizures/4 weeks | Standard Deviation 5.84 |
| PPS - Baseline Period | Change From Baseline in Standardized Seizure Frequency | 4.0 seizures/4 weeks | Standard Deviation 3.54 |
| PPS- Treatment Period | Change From Baseline in Standardized Seizure Frequency | 3.1 seizures/4 weeks | Standard Deviation 5.64 |