Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study)
Condition: Epilepsy; Paediatric Partial Onset Seizures
MeSH terms: Epilepsy; Seizures
Intervention: Zonisamide; Placebo
Intervention description: 8mg/kg per day for approximately 24 weeks.
Intervention MeSH terms: Zonisamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 207.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Epilepsy; paediatric; partial onset seizures

Summary:

      The purpose of this study is to compare the safety and efficacy of zonisamide with placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is male or female aged 6-17 years inclusive.

          2. Parent/guardian is willing to sign an approved informed consent form, and accompany
             the subject on all study visits.

          3. Subject is willing to give informed (written or verbal) assent and if appropriate
             written informed consent.

          4. Subject has a clinical diagnosis of epilepsy with partial-onset seizures with or
             without secondary generalized seizures according to the International League Against
             Epilepsy's Classification of Epileptic Seizures (1981).

          5. Diagnosis has been established by clinical history, electroencephalogram (EEG) and
             computed tomography/ magnetic resonance imaging (CT/MRI) of the brain consistent with
             localization related epilepsy.

          6. Subject has > four (simple or complex) partial seizures (with or without secondary
             generalization) per month over the eight week Screening Period with at least one
             seizure in each four week period and with no 21 day period being seizure free.

          7. Subject is taking a stable regimen of one or two other AEDs for at least one month
             prior to Visit 1 (start of the Screening Period).

             NOTE: If using a vagal nerve stimulator (VNS), it must have been implanted for at
             least five months and stimulator parameters must remain unchanged for at least one
             month prior to Visit 1 (start of the Screening Period), and throughout the entire
             study period. VNS will be considered as one AED for the purposes of this study.

          8. Subject is in general good health as determined by medical history, physical exam and
             screening laboratory results.

          9. Parent/guardian is willing and able to complete a seizure diary for the duration of
             the study.

        Exclusion Criteria:

          1. Subject of body weight < 20 kg at the Screening Visit.

          2. Subject is unable to swallow capsules.

          3. Subject has progressive neurological disease (determined by diagnosis or a
             pre-existing brain image such as a CT scan or MRI).

          4. Subject has a history of idiopathic generalized epilepsy as defined by the
             International League Against Epilepsy (ILAE).

          5. Subjects with Lennox-Gastaut syndrome, absence, myoclonic, clonic and/or tonic (other
             than secondary generalized) and atonic seizures.

          6. Subject has psychogenic seizures

          7. Subject has a history of status epilepticus within a year of the Screening Visit
             whilst taking AEDs.

          8. Subject has seizures that only occur in clustered patterns, or has seizures that are
             too close together to count accurately.

          9. Subject has a history of renal calculi or renal insufficiency (creatinine levels >194
             µmol/l (1.5 mg1/dl).

         10. Subject had a predisposing condition that might interfere with absorption,
             distribution, or excretion of zonisamide.

         11. Subject has a history of psychiatric illness.

         12. Subject has a history of suicide attempt.

         13. Female subject who is pregnant or lactating.

         14. Subject has a history of demonstrated non-compliance with treatment or, the subject,
             parent or legal guardian can be reasonably expected not to be compliant with study
             procedures or to complete the study.

         15. Female subject of 10 years of age or greater or of child bearing potential (i.e.,
             started menses) and is not taking or prepared to take a medically acceptable form of
             contraception (i.e., oral contraceptive pill, surgical sterilization, an implant or an
             injected form of contraception, or intrauterine device), or who is not prepared to
             abstain from sexual activity for the duration of the study and one month after last
             administration of study medication.

             NOTE: Should a female subject become of childbearing potential during the study, they
             must be reconsented in order to give consent to undergo pregnancy testing and either
             confirm abstinence or receive medically appropriate form of contraception.

         16. Subject has clinically significant abnormal laboratory values at the Screening Visit.

         17. Subject has received previous treatment with zonisamide.

         18. Subject is treated with a ketogenic diet or is likely to have surgery for epilepsy in
             the trial period.

         19. Subject requires frequent rescue benzodiazepines (> than once per week).

         20. Concomitant use of felbamate or use of felbamate within 2 months prior to Visit 1.

         21. Subject has elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate
             aminotransferase (AST) > 2 times the upper limit of normal (ULN).

         22. Subject has evidence of significant active and unstable haematological disease; i.e.,
             white blood cell (WBC) count < 2500/µL or an absolute neutrophil count < 1000/µL

         23. Subject with clinically significant active hepatic disease, cardiovascular, metabolic,
             respiratory, renal, endocrinological and gastrointestinal diseases or any other
             clinically significant organic disease, within 30 days prior to the Screening Visit.

         24. Subjects with known or suspected history of alcoholism or drug abuse within the
             previous two years, or a positive finding on urinary drug screening of any drugs other
             than prescribed medications.

         25. Subjects with any other condition that would make them, in the opinion of the
             Investigator unsuitable for this study.

         26. Subjects who have participated in a clinical trial involving administration of an
             investigational compound (including zonisamide) within three months of the Screening
             Visit.

         27. Subjects with a known or suspected hypersensitivity to zonisamide, or sulphonamides.

         28. Subjects taking acetazolamide, any carbonic anhydrase inhibitors e.g. topiramate, and
             any drugs with anticholinergic activity.

         29. Subjects who do not have a complete seizure diary during the Screening Period.

         30. Subjects with active and/or insufficiently treated neurocysticerosis or intercraniel
             tubiculosis. Note: subjects who have completed a curative antihelminthic or
             antituberculous treatment course more than 3 months before screening and who are free
             of signs and symptoms of active infection (including on a post treatment CT/MRI scan),
             may be enrolled in the study.

         31. Subjects taking antipsychotics, monoamine oxidase inhibitors (MAOIs), tricyclic
             antidepressants (TCAs) and benzodiazepines with barbiturates and amphetamines for
             disease other than epilepsy within 3 months of screening.