An add-on Study of E2007 in Patients With Refractory Partial Seizures Uncontrolled With Other Anti-epileptic Drugs (AEDs)
Condition: Refractory Partial Seizures
MeSH terms: Seizures
Intervention: E2007
Intervention description: The dose of E2007 will start from 2 mg and will be increased by 2 mg every week up to 12 mg (the maximum dose). The dose will be adjusted during 6 weeks (i.e., titration period). Subsequently, the dose will be fixed and maintained during 4 weeks (Maintenance period). Patients must visit study site at Weeks -4, 1, 2, 3, 4, 5, 6, 8, 10 and 14 to confirm.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 20 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Seizures; epilepsy

Summary:

      The purpose of this study is to explore the maximum tolerated dose of E2007 in Japanese
      patients with refractory partial seizures which are uncontrolled with other anti-epileptic
      drugs (AEDs). Thirty patients will receive E2007 (dose escalating to the maximum of 12 mg per
      day). The dose of E2007 will be adjusted during 6 weeks. Subsequently, the dose will be fixed
      and maintained during 4 weeks.
    

Eligibility criteria:

        Inclusion criteria:

          1. Male or female aged between 20 and 64 years old.

          2. Patients diagnosed with partial seizure (including secondarily generalized seizure).

          3. Patients who have at least 3 counts of partial seizures during the previous 4 weeks
             prior to observation start and no seizure-free for 21 days during 8 weeks before the
             treatment start based on medical records. Simple partial seizure without motor signs
             will not be counted.

          4. Patients who have been treated for at least 12 weeks but confirmed to be uncontrolled
             with more than one standard AED for 2 years.

          5. Patients treated with stable doses of up to three AEDs. Only one cytochrome

             P450 (CYP) 3A4 inducer shown below will be allowed for concomitant use:

               -  Carbamazepine

               -  Phenytoin

               -  Phenobarbital

               -  Primidone

          6. Patients on stable dose of anti-depressants, anti-anxiety drugs, or mood stabilizers
             from before 8 weeks.

        Exclusion criteria:

          1. Patients with present or a history of Lennox-Gastaut syndrome.

          2. Patients with present generalized seizures (e.g., absence, myoclonic).

          3. Patients with a history of status epilepticus within 1 year.

          4. Patients with seizure clusters where individual seizure cannot be counted within 8
             weeks.

          5. Patients with a history of psychogenic seizure.

          6. Patients who underwent surgical operation for epilepsy within 2 years.

          7. Patients using rescue benzodiazepines at least twice in a 4-week duration within 8
             weeks (if 1 or 2 doses over 24-hour period considered one-time rescue).

          8. Patients whose alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at
             enrollment in observation period exceeds 1.5-fold the upper limit of normal (ULN), but
             those whose ALT or AST are constantly higher than ULN, they can enroll if ALT or AST
             remain in 3-fold the ULN.

          9. Patients with significant active hematological disease; white blood cell (WBC) count
             </=2500/uL or neutrophil count </=1000 uL.

         10. Patients on anti-psychotics or who have psychotic disorder and/or psychotic
             disorder(s) or unstable recurrent affective disorder(s) with a history of suicidal
             attempt within 2 years.

         11. Patients who operate heavy equipment or drive should not be recruited into the study.