Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures
Condition: Partial Epilepsy
MeSH terms: Epilepsy; Seizures; Epilepsies, Partial
Intervention: 800 mg QD Eslicarbazepine acetate; 1200 mg QD Eslicarbazepine acetate; Placebo
Intervention description: Oral, 800 mg QD, 2-week titration period and 12-week maintenance period; Oral, 1200 mg QD, 2-week titration followed by 12-week maintenance period; Placebo tablet given 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: 653.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Refractory; partial; epilepsy; efficacy; eslicarbazepine; safety

Summary:

      The purpose of this study is to determine whether Eslicarbazepine acetate (BIA 2-093) is an
      effective adjunct therapy in the treatment of refractory partial seizures
    

Eligibility criteria:

        Inclusion Criteria

        At V1 (screening), patient must be/have:

          1. Written informed consent signed by patient.

          2. Aged 16 years or more (patients under 18 years of age require parental/legal
             representative consent). In North America as well as in other participating countries,
             when appropriate and/or required by state or local law, minor patients must give
             written informed assent prior to participation in the study.

          3. A documented diagnosis of epilepsy since at least 12 months prior to screening.

          4. At least 4 partial-onset seizures (including subtypes of simple partial, complex
             partial and partial seizures evolving to secondarily generalised) on the 4 weeks prior
             to screening.

          5. Currently treated with 1 or 2 AEDs (any except OXC), in a stable dose regimen during
             at least 1 month prior to screening. Patients using vigabatrin should have been on
             this medication for at least 1 year with no deficit in visual field identified (a
             confirmatory test should be available within 1 month before study entry). The device
             for VNS should be implanted at least 6 months before screening; parameters need to be
             stable for at least 1 month prior to screening (VNS will not be counted as concomitant
             AED).

          6. Excepting epilepsy, patient is judged to be in general good health based on medical
             history, physical examination findings, and clinical laboratory test results.

          7. Post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or
             tubal ligation. In case of women of childbearing potential (WOCBP), patient must
             present a serum beta-human chorionic gonadotropin (B-hCG) test consistent with a non
             gravid state and agree to remain abstinent or use reliable contraception (hormonal
             contraception should be combined with a barrier method) beginning at screening and
             continuing at least to the PSV.

             At V2 (randomisation), patient must have:

          8. At least 8 partial-onset seizures during baseline with at least 3 partial-onset
             seizures in each 4-week section of the 8-week baseline period prior to randomisation
             (documented in a diary) and no seizure-free interval exceeding 28 consecutive days.

          9. In case of WOCBP, patient must present a urine B-hCG test consistent with a non gravid
             state.

         10. Diaries satisfactorily completed by the patient or his/her caregiver.

         11. Satisfactorily complied with the study requirements during the baseline period
             (including no changes in concomitant AED therapy should have occurred in the baseline
             period).

        Exclusion Criteria

        At V1 (screening), patients must not be/have:

          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 cerebral lesion).

          4. Occurrence of seizures too close to count accurately.

          5. History of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30
             minutes) within the 3 months prior to screening.

          6. Seizures of non-epileptic origin.

          7. Seizures of psychogenic origin within the last 2 years.

          8. Major psychiatric disorders.

          9. Documented diagnosis of schizophrenia with accompanying documented history of at least
             1 acute psychosis episode within the last 2 years) or history of suicide attempt.

         10. Currently treated with OXC.

         11. Using benzodiazepines on more than an occasional basis (defined as more than 2 times
             per week), except when used chronically as AED.

         12. Known exposure to Eslicarbazepine acetate from previous study.

             o Previous use of Eslicarbazepine acetate or participation in a clinical study with
             Eslicarbazepine acetate (patients not exposed to Eslicarbazepine acetate [e.g., screen
             failed] are allowed).

         13. Known hypersensitivity to carboxamide derivatives.

         14. History of abuse of alcohol, drugs or medications within the last 2 years.

         15. Uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic,
             haematological or oncology disorder.

         16. Second or third-degree atrioventricular blockade not corrected with a pacemaker.

         17. Relevant clinical laboratory abnormalities (e.g., sodium <130 mmol/L, alanine or
             aspartate transaminases >2.0 times the upper limit of the normal, white blood cell
             [WBC] count <3,000 cells/mm3) or for patients of Asian ancestry, positive HLA B*1502
             test.

         18. Estimated creatinine clearance <60 mL/min [men: (140-age) x weight/serum creatinine x
             72; women: (0.85) (140-age) x weight/serum creatinine x 72. Age in years, weight in
             kg, and serum creatinine in mg/dL].

         19. Pregnant or nursing.

         20. Participation in other drug clinical trial within the last 2 months or received an
             investigational drug within 5 half-lives of this other product, whichever is longer.
             Patient(s) who are known to have not taken any doses of study drug(s) in earlier
             study(ies) (e.g. screen-failures) are allowed without any time limitation.

         21. Not ensured capability to perform the trial.

         22. Any other condition or circumstance that, in the opinion of the Investigator, may
             compromise the patient's ability to comply with the study protocol.

         23. Currently treated with VNS, but implanted <6 months before screening or parameters not
             stable for at least 1 month prior to screening.

             At V2 (randomisation), patients must not be/have:

         24. Inadequate compliance to concomitant AEDs during the 8-week baseline period or to
             screening exclusion criteria.

         25. Inadequate completion of the study diary.

         26. Any other condition or circumstance that, in the opinion of the Investigator, may
             compromise the patient's ability to comply with the study protocol.