Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs
Condition: Epilepsy With Simple or Complex Partial Onset Seizures
MeSH terms: Epilepsy; Seizures; Epilepsies, Partial
Intervention: Eslicarbazepine acetate; Eslicarbazepine acetate
Intervention description: 1600 mg QD; 1200 mg QD
Intervention MeSH terms: Eslicarbazepine acetate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 193.0
Sex: All
Minimum age: 16 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Seizure; Epilepsy; Anticonvulsant; Historical Control; Monotherapy

Summary:

      This is an 18-week, double-blind, multicenter study with gradual conversion from previous
      antiepileptic therapy to eslicarbazepine acetate monotherapy in subjects with partial
      epilepsy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of partial epilepsy as defined in the Classification of Seizures of the
             International League Against Epilepsy (ILAE) (simple partial seizures with observable
             motor component, or complex, with or without secondary generalization) a. Medical
             history of seizures; b. Absence of confounding factors (pseudoseizures, syncope); c.
             Documented EEG recording (done within 5 years prior to screening) consistent with
             focal onset epilepsy.

          -  Documented CT or MRI scan conducted within 10 years prior to screening, showing the
             absence of a progressive structural abnormality (eg, tumor). Mesial temporal sclerosis
             is acceptable.

          -  ≥4 partial onset seizures during the 8 weeks prior screening with no 28-day seizure
             free period.

          -  Stable treatment with 1-2 AEDs during the last 4 weeks prior to screening.

          -  Subjects must have the ability to comprehend the informed consent form and be willing
             to provide informed consent. For subjects who are unable to comprehend the written
             consent, a witness/caregiver who is able to describe and provide an understanding of
             the informed consent to the subject must sign the consent form on behalf of the
             subject.

          -  Subjects must give written informed consent prior to participation in the study. For
             subjects <18 years of age, the informed consent must be signed by the subject's parent
             or legal guardian, and, when appropriate and/or required by state or local law, minor
             subjects must give written informed assent prior to participation in the study.
             Subjects of Asian ancestry are required to give written informed consent for
             genotyping. All subjects must sign a HIPAA Form. All females of child bearing
             potential must also sign the "Women of Childbearing Potential" Addendum.

          -  A female subject is eligible to enter and participate in the study if she is of: a.
             Non-childbearing potential (ie, physiologically incapable of becoming pregnant,
             including any female who is pre-menarchal or post-menopausal); b. Child-bearing
             potential (all females ≤65 years of age), has a negative pregnancy test at screening
             and agrees to satisfy contraception requirements.

        Exclusion Criteria:

          -  Subjects with only simple partial seizures without a motor component.

          -  Presence of generalized seizure syndromes (eg, juvenile myoclonic epilepsy or
             Lennox-Gastaut syndrome).

          -  History of pseudo-seizures.

          -  Current seizures related to an acute medical illness.

          -  Seizures secondary to metabolic, toxic or infectious disorder or drug abuse.

          -  Status epilepticus within 2 years prior to screening.

          -  Seizures only occurring in a cluster pattern.

          -  Subjects taking 2 of the following sodium channel blocking AEDs: phenytoin,
             carbamazepine, oxcarbazepine, or lamotrigine.

          -  Subjects taking 2 AEDs with both being in the upper dose range (defined as
             approximately two-thirds of the defined daily dose).

          -  Subjects taking more than 2 AEDs.

          -  Subjects with progressive structural central nervous system lesion or progressive
             encephalopathy.

          -  Psychiatric exclusion criteria: subjects with history of suicide attempt in last 2
             years; major depressive episode within last 6 months; abuse of alcohol or substance
             abuse in last 2 years; significant psychiatric disorder or recurrent episodes of
             severe depression within 2 years prior to screening.

          -  Medical exclusion criteria: known renal insufficiency or subject with estimated
             creatinine clearance [CrCL] <60 mL/min based on serum creatinine using the
             Cockcroft-Gault formula.

          -  Clinical and laboratory exclusion criteria: Subjects of Asian ancestry who tests
             positive for the presence of the HLA-B*1502 allele.

          -  Subjects who have been on benzodiazepines, phenobarbital, or primidone on a regular
             basis within 3 months prior to screening.

          -  Subjects taking antipsychotics, tricyclic antidepressants, anxiolytics, sedative
             hypnotics including non-benzodiazepines, central opioid agonists/antagonists,
             monoamine oxidase inhibitors (MAOIs) within at least 5 half lives (or for at least 2
             weeks whichever is longer) prior to randomization.

          -  Subjects presently on felbamate or vigabatrin

          -  Female subjects who are currently breastfeeding or intending to breastfeed during
             study period.