A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy
Condition: Epilepsy
MeSH terms: Epilepsy; Epilepsies, Partial
Intervention: Zonisamide; Carbamazepine
Intervention description: Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.; Week 1 and 2 either 100mg zonisamide or 200 mg carbamazepine Week 3 and 4 either 200mg zonisamide or 4800 mg carbamazepine Week 5 and 6 either 300mg zonisamide or 600 mg carbamazepine; this dose then to be maintained unless a subject has a seizure more than two weeks post a dose increase.
Intervention MeSH terms: Carbamazepine; Zonisamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 583.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Epilepsy

Summary:

      This is a two-arm, randomized, double-blind, non-inferiority study using a flexible dosing
      regime to allow optimal zonisamide or carbamazepine therapy for individual subjects.
      Assessment of eligibility will take place at the Screening Visit. The subjects will be
      randomized to either the carbamazepine or zonisamide arm at the Randomization Visit (T1). T1
      must occur as soon as possible (and at least within 14 days) of the Screening Visit in order
      to optimize subject care.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        Subjects will be eligible for the study if they meet all of the following inclusion
        criteria:

          1. Male or female subjects, 18 to 75 years of age inclusive.

          2. Subjects with untreated, newly diagnosed epilepsy having at least two well documented,
             unprovoked, clinically evaluated and classified partial seizures (with or without
             secondary generalization) or generalized tonic-clonic seizures (without clear focal
             origin) within 12 months of the Screening Visit, of which at least one seizure
             occurred within three months of the Screening Visit (> one seizure within a 24 hour
             period will be counted as one seizure).

          3. Subjects will either have had no previous use of an AED, or treatment with one AED for
             a maximum duration of two weeks before the Randomization Visit (T1).

          4. Subjects have a documented electroencephalogram (EEG) within 12 months of the
             Screening Visit, compatible with localization-related epilepsy (to exclude primary
             generalized epilepsy).

          5. Subjects have a documented computed axial tomography (CAT) scan or magnetic resonance
             imaging (MRI) scan confirming the absence of a progressive neurological lesion within
             12 months of the Screening Visit.

          6. Female subjects without childbearing potential (two years post-menopausal, bilateral
             oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects
             with childbearing potential must not be pregnant as confirmed by a negative pregnancy
             test at screening and randomization, must not be lactating and must be using a
             medically acceptable form of contraception, for the duration of the study and for one
             month following discontinuation of the study drug. Medically acceptable contraception
             is defined here as oral contraception pill with at least 50 micrograms
             ethinylestradiol per intake, contraceptive injections and implants, or intrauterine
             device in place for at least three months.

          7. Subjects who are able and willing to follow investigational study procedures, maintain
             a seizure diary, and report AEs.

          8. Subjects who are able and willing to give written informed consent.

        EXCLUSION CRITERIA:

        Subjects who meet any of the following exclusion criteria will not be eligible for the
        study:

          1. Subjects have a history of clinical investigations, including EEG data, that are
             suggestive of idiopathic generalised epilepsy as defined by the International League
             Against Epilepsy (ILAE).

          2. Subjects with a history of absence, myoclonic, clonic, tonic, or atonic seizures.

          3. Subjects have a history of status epilepticus, and/or non-epileptic seizures (e.g.,
             metabolic, pseudo-seizures).

          4. Subjects have experienced seizures relating to drugs, alcohol, acute medical illness,
             mental retardation, or subjects with situation-related seizures.

          5. Subjects have progressive encephalopathy or findings consistent with progressive CNS
             disease or lesion (e.g. infection, demyelination, or tumour).

          6. Subjects have a history of a significant or currently uncontrolled disease that will
             interfere with the conduct of this study or the assessment of safety and efficacy of
             the study drug.

          7. Subjects have been previously treated with carbamazepine or zonisamide.

          8. Subjects have received an investigational drug or device in the three months prior to
             the Screening Visit.

          9. Subjects have a known hypersensitivity to sulfonamides, dibenzazepine derivatives, or
             tricyclic antidepressants.

         10. Subjects have a history of bone marrow depression, low platelet count or other blood
             dyscrasia.

         11. Subjects have a history of acute intermittent porphyria.

         12. Subjects have a history of renal disorder (serum creatinine level of > 135 Ã¬mol / l
             (1.5 mg/dL at the Screening Visit), hepatic disorder or clinically significant
             abnormal liver function tests; aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) >2 times the upper normal limit.

         13. Subjects have a body weight of less than 40 kg.

         14. Subjects have a history of progressive malignancy within the previous 5 years
             (excluding a history of non-metastasized and adequately treated cutaneous squamous
             cell carcinoma).

         15. Subjects have a history of psychiatric illness or mood disorder requiring
             electro-convulsive or drug therapy within the previous 6 months which is considered
             uncontrolled; a history of suicide attempt; alcohol or drug abuse; chronic treatment
             with benzodiazepines or barbiturates.

         16. Subjects are currently taking carbonic anhydrase inhibitors.

         17. Subjects have a history of pancreatitis, nephrolithiasis or hypercalcuria, clinically
             significant laboratory or electro-cardiographic abnormalities, or uncontrolled
             hypertension.

         18. Subjects are currently taking mono-amine oxidase inhibitors (MAOIs) or any other
             excluded medications.