A Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures
Condition: Epilepsy
MeSH terms: Seizures
Intervention: Zonisamide at targeted daily doses of 100-500 mg/day; Placebo administered to match targeted daily doses of 100-500 mg/day
Intervention description: Each group received 2 doses a day (in the morning and evening) during the Titration Period, once a day (in the evening) or BID during the Maintenance Phase, comprising 25 mg, 50 mg, or 100 mg of ZNS capsules; matching placebo
Intervention MeSH terms: Zonisamide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 41.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      A two arm, randomized, double-blind study comparing zonisamide with placebo. The zonisamide
      arm will consist of 100 subjects and the placebo arm of 50 subjects. Study medication will be
      administered as an add-on treatment to the subject's current 1 or 2 anti-epileptic (AEDs).
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Capable of maintaining a seizure daily diary or who have access to a caregiver who is
             prepared to complete this on the patient's behalf.

          2. Able to complete the questionnaires used in this study.

          3. Localization related epilepsy, with simple and/or complex partial seizures with or
             without secondary generalized seizures as defined by the International League Against
             Epilepsy (ILAE) criteria.

          4. Have at least one well documented seizure in the 4 weeks preceding the Randomisation
             Visit (Visit 2) and are deemed to require additional AED medication.

          5. Receiving at least one, but not more than two other marketed AEDs as concomitant
             medication, and the dosage should be stable for at least four weeks before the
             Screening Visit.

        Key Exclusion Criteria:

          1. Seizures attributed to metabolic causes (e.g., electrolyte disturbances,
             hyperglycaemia).

          2. Seizures which could be attributed to use of a drug.

          3. Presence of primary generalised epilepsies or seizures, such as absences, myoclonic
             epilepsies, Lennox-Gastaut syndrome.

          4. A history of eating disorders or a body weight below 40 kg.

          5. A history of blood dyscrasias.

          6. A history of renal stones or having risk factors for nephrolithiasis such as a family
             history of nephrolithiasis or hypercalciuria.

          7. An increased risk factor for rhabdomyolysis such as uncontrolled hypothyroidism,
             personal or family history of muscle disorders.

          8. Taking concomitant medication associated with nephrolithiasis and medications
             increasing the risk of rhabdomyolysis.

          9. Taking rifampicin or drugs with anticholinergic effects.

         10. Taking carbonic anhydrase inhibitors or topiramate.

         11. A history of pancreatitis.

         12. A history of Stevens Johnson Syndrome.

         13. Elevated levels of serum creatinine >165 Umol, or known severe hepatic impairment to
             the extent that the protocol dose titration schedule cannot be followed.