A Study of a Drug to be Used in Addition With Another Drug to Treat Adults With Uncontrolled Partial-onset Seizures
Condition: Epilepsy With Partial On-set Seizures
MeSH terms: Epilepsy; Seizures
Intervention: Eslicarbazepine acetate; Eslicarbazepine Acetate
Intervention description: eslicarbazepine acetate tablets, taken once daily. Subjects begin 2-week Titration Phase starting on Day 1 (Week 1), by initiating treatment with ESL 400 mg/day. Subjects titrate to minimum dose of 800 mg/day for the 24-week Maintenance Phase beginning at Week 3. In the Maintenance Phase, subjects may titrate in weekly increments of 400 mg/day as medically indicated at the discretion of Investigator up to a maximum dose of 1200 mg/day (Canadian sites) or 1600 mg/day (US sites); eslicarbazepine acetate acetate tablets, taken once daily. Subjects begin 2-week Titration Phase starting on Day 1 (Week 1), by initiating treatment with ESL 400 mg/day. Subjects titrate to minimum dose of 800 mg/day for the 24-week Maintenance Phase beginning at Week 3. In the Maintenance Phase, subjects may titrate in weekly increments of 400 mg/day as medically indicated at the discretion of Investigator up to a maximum dose of 1200 mg/day (Canadian sites) or 1600 mg/day (US sites)
Intervention MeSH terms: Eslicarbazepine acetate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Arm 1 (ESL as first add-on) Arm 2 (ESL as later add-on)
Masking: None (Open Label)
Masking description: open label
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: epilepsy; seizures; partial on-set seizures

Summary:

      A study of a drug to be used in addition with another drug to treat adults with Uncontrolled
      Partial-onset Seizures
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects ≥ 18 years of age.

          2. Subject is willing and able to sign informed consent.

          3. Subject has a documented diagnosis of epilepsy with simple POS with a motor component
             or complex POS with or without secondarily generalized seizures as defined in the
             Classification of Seizures of the International League Against Epilepsy

          4. Subject has a documented electroencephalogram within 10 years prior to screening.

          5. Subject has had at least 3 POS during previous six months.

          6. Subject has had a sufficient number of seizures at time of enrollment to justify
             adjunctive therapy, as determined by the Investigator.

          7. Subjects are required to be ESL-naïve AND

               1. Maintained on a stable LEV or LTG regimen for at least 1 month (28 days) prior to
                  screening with no history of adjunctive treatment (for Arm 1, ESL as first
                  add-on).

                  OR

               2. Maintained on a stable dose of 1-2 AEDs (excluding OXC) for at least 1 month (28
                  days) prior to screening and who have had prior adjunctive treatment (for Arm 2,
                  ESL as later add-on).

          8. If the subject is treated with any stimulation device for epilepsy Vagal Nerve
             Stimulation (VNS), Responsive Neurostimulator (RNS), or similar, the device must have
             been implanted at least 6 months before screening and the device parameters must be
             documented as stable for at least 1 month prior to screening. (Note: These devices
             will not be counted as concomitant AED).

          9. Except for epilepsy, subject is judged to be in general good health based on medical
             history, physical examination findings, and clinical laboratory

        Exclusion Criteria:

          1. Subjects with a prior exposure to ESL.

          2. Subjects currently being treated with OXC.

          3. Subject with a history of allergic reaction to OXC or CBZ, or a history of serious
             allergic reaction (Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and
             Systemic Symptoms or similar) to any AED, or a history of serious allergic reactions
             to other medications.

          4. Subjects who have taken warfarin, felbamate, vigabatrin, or perampanel, (unless at
             stable dose with safety testing for ≥ 1 year) within a 4-week period prior to
             screening.

          5. Subjects taking ezogabine

             .

          6. Subject has taken any medication prohibited for this protocol within 4 weeks prior to
             Screening

          7. Subjects using benzodiazepines on more than an occasional basis (defined as more than
             2 times per week), except when used chronically as an AED

          8. Seizure disorder characterized primarily by simple POS without motor signs.

          9. Subject has a history of primarily generalized seizures (eg, myoclonic, absence,
             tonic).

         10. Subject has a history of status epilepticus or cluster seizures (ie, 3 or more
             seizures within 30 minutes) within the 3 months prior to screening.

         11. Subject has had seizures of psychogenic origin or purely subjective seizures within
             the last 2 years.

         12. Subject has had seizures too close to count accurately.

         13. Subject has a known progressive structural central nervous system (CNS) lesion,
             progressive encephalopathy or any other condition that may result in epilepsy
             secondary to a cerebral abnormality.

         14. Subject whose current seizures are related to an acute medical illness or other
             non-epileptic origin.

         15. Subjects of Asian ancestry will be excluded if they are carriers of HLA-B*1502.
             Either:

               1. Subject must give written informed consent for genotyping, and test negative. OR

               2. Subjects must provide documentation of prior testing confirming non-carrier
                  status.

         16. Subject has a major medical illness other than epilepsy that would prevent safe
             participation in this study, at the discretion of the Investigator, including (but not
             limited to) cardiac disease, thyroid disease, hepatic or renal impairment, endocrine
             or metabolic disease, gastrointestinal disease, or hematologic disease. Note: Active
             medical conditions that are minor or well-controlled are not exclusionary if they do
             not affect risk to the subject or the study results. If the effect of the condition in
             regard to the risk to the subject or to the study results is unclear, the Medical
             Monitor should be consulted.

         17. Subjects with clinically relevant laboratory abnormalities at screening (eg, sodium <
             130 mEq/L, alanine transaminase (ALT) or aspartate transaminase (AST) > 2.0 times the
             upper limit of the normal, white blood cell [WBC] count < 3,000 cells/mm3, estimated
             creatinine clearance < 50 mL/min, or has values for thyroid testing (free
             triiodothyronine (T3), free thyroxine (T4), thyroid stimulating hormone [TSH])
             indicating the presence of significant thyroid dysfunction.

         18. Subject has a history or presence of abnormal electrocardiogram (ECG), which in the
             Investigator's opinion is clinically significant or QT interval corrected for heart
             rate using the Fridericia method (QTcF) of ≥ 450 msec per screening ECG.

         19. Subject has second or third-degree atrioventricular block that is not corrected with a
             pacemaker.

         20. Subjects who meet the Diagnostic and Statistical Manual of Mental Disorders, 5th
             edition text revision defined criteria for major depressive episode within the last 6
             months. Subjects with mild, chronic depression without recent hospitalization who are
             being maintained on a stable dose of a single antidepressant are acceptable.

         21. Subject has an active suicidal plan or intent (in the Investigator's opinion) in the
             past 4 weeks prior to screening.

         22. Subject has a history of suicide attempt in the last 2 years prior to screening.

         23. Subject has other major psychiatric disorders.

         24. Subjects who are not able to complete the diary in the Investigator's opinion.

         25. Subject has a history of alcohol or substance abuse within 2 years prior to screening
             for study participation, or subjects currently using alcohol, drugs of abuse, or any
             prescribed or over-the-counter medication in a manner, which, in the opinion of the
             Investigator, indicates abuse.

         26. Subject tests positive for drugs of abuse at screening. Note: Subjects with a positive
             drug screen for marijuana, amphetamines, opiates, or benzodiazepines, who have a
             documented prescription for a medical condition and are on a stable dose of this
             prescribed medication for at least 4 weeks prior to screening, may be eligible to
             participate in the study upon approval from the Medical Monitor.

         27. Subject is pregnant, currently nursing, or intends to become pregnant during the study
             period or within 30 days of the last dose of study drug.

         28. Subject has participated in any investigational study within 30 days prior to
             screening, as documented in subject's medical history.

         29. Subject is a clinical or investigational site staff member or relative of a staff
             member.

         30. Any other condition or circumstance that, in the opinion of the Investigator, may
             compromise the subject's ability to comply with the study protocol.