Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures
Condition: Refractory Partial Epilepsy
MeSH terms: Epilepsy; Seizures; Epilepsies, Partial
Intervention: eslicarbazepine acetate; placebo
Intervention description: once-daily oral tablet; once daily placebo comparator
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: 402.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory; partial; epilepsy

Summary:

      This was a phase III 4-part study in multiple centres. Part I was a 26-week parallel-group,
      randomised, placebo-controlled period (8 weeks single-blind placebo baseline, 2 weeks
      double-blind titration, 12 weeks maintenance, and 4 weeks tapering off). After completing the
      baseline period, patients were randomised in a 1:1:1:1 ratio to 1 of 3 ESL dose levels or to
      placebo. Part II was a 1-year open-label extension for patients who had completed Part I. The
      starting dose was 800 mg once daily and could be titrated up or down at 400-mg intervals
      between 400 and 1200 mg. Part III was an additional 1-year open-label extension for patients
      who had completed Part II, had participated in the post-Part II study extension, which
      allowed patients to continue treatment with ESL, or had continued to take ESL in a
      compassionate use program. ESL starting doses were the same as received at the end of Part
      II, during post-Part II study extension, or under compassionate use, and could be titrated up
      or down at 400-mg intervals between 400 and 1200 mg once daily. Part IV was a study extension
      to allow patients to continue ESL treatment after the end of Part III until marketing
      authorisation or discontinuation of clinical development.
    

Eligibility criteria:

        Inclusion Criteria:

          -  written informed consent signed by patient

          -  aged 18 years or more

          -  documented diagnosis of simple or complex partial seizures with or without secondary
             generalisation since at least 12 months prior to screening

          -  at least 4 partial seizures in each 4 week period during the last 8 weeks prior to
             screening, currently treated with 1 or 2 AEDs (any except oxcarbazepine and
             felbamate), in a stable dose regimen during at least 2 months prior to screening
             (patients using vigabatrin should have been on this medication for at least 1 year
             with no deficit in visual field identified)

          -  excepting epilepsy, patient is judged to be in general good health based on medical
             history, physical examination and laboratory tests

          -  post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or
             tubal ligation; in case of woman of childbearing potential, patient must present a
             serum beta-hCG test consistent with a non-gravid state and agree to remain abstinent
             or use reliable contraception (oral contraception should be combined with a barrier
             method)

        Exclusion Criteria:

          -  only simple partial seizures with no motor symptomatology (classified as A2-4
             according to the International Classification of Epileptic Seizures) that are not
             video-EEG documented

          -  primarily generalised epilepsy

          -  known rapid progressive neurological disorder; history of status epilepticus or
             cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months
             prior to screening

          -  seizures of psychogenic origin within the last 2 years

          -  history of schizophrenia or suicide attempt

          -  currently on or with exposure to felbamate or oxcarbazepine more within one month of
             screening

          -  using benzodiazepines on more than on an occasional basis (except when used
             chronically as AED)

          -  previous use of ESL or participation in a clinical study with ESL

          -  known hypersensitivity to carbamazepine, oxcarbazepine or chemically related
             substances

          -  history of abuse of alcohol, drugs or medications within the last 2 years

          -  uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic,
             haematological or oncology disorder

          -  second or third-degree atrioventricular blockade not corrected with a pacemaker

          -  relevant clinical laboratory abnormalities