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

Eisai

Status and phase: Terminated; Phase 4

Conditions: Epilepsy

Treatments: Drug: Zonisamide at targeted daily doses of 100-500 mg/day; Drug: Placebo administered to match targeted daily doses of 100-500 mg/day

Study type: Interventional

Funder types: Industry

Identifiers

NCT01546688

E2090-E044-402

2006-002516-10 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 41 patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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41 participants in 2 patient groups, including a placebo group

Zonisamide at targeted daily doses of 100-500 mg/day

Active Comparator group

Treatment:

Drug: Zonisamide at targeted daily doses of 100-500 mg/day

Placebo administered to match daily doses of 100-500 mg/day

Placebo Comparator group

Treatment:

Drug: Placebo administered to match targeted daily doses of 100-500 mg/day