A Double-blind Study to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy

INCLUSION CRITERIA: Subjects will be eligible for the study if they meet all of the following inclusioncriteria:

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 withoutsecondary generalization) or generalized tonic-clonic seizures (without clear focalorigin) within 12 months of the Screening Visit, of which at least one seizureoccurred within three months of the Screening Visit (> one seizure within a 24 hourperiod will be counted as one seizure).

3. Subjects will either have had no previous use of an AED, or treatment with one AED fora maximum duration of two weeks before the Randomization Visit (T1).

4. Subjects have a documented electroencephalogram (EEG) within 12 months of theScreening Visit, compatible with localization-related epilepsy (to exclude primarygeneralized epilepsy).

5. Subjects have a documented computed axial tomography (CAT) scan or magnetic resonanceimaging (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, bilateraloophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjectswith childbearing potential must not be pregnant as confirmed by a negative pregnancytest at screening and randomization, must not be lactating and must be using amedically acceptable form of contraception, for the duration of the study and for onemonth following discontinuation of the study drug. Medically acceptable contraceptionis defined here as oral contraception pill with at least 50 microgramsethinylestradiol per intake, contraceptive injections and implants, or intrauterinedevice in place for at least three months.

7. Subjects who are able and willing to follow investigational study procedures, maintaina 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 thestudy:

1. Subjects have a history of clinical investigations, including EEG data, that aresuggestive of idiopathic generalised epilepsy as defined by the International LeagueAgainst 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 CNSdisease or lesion (e.g. infection, demyelination, or tumour).

6. Subjects have a history of a significant or currently uncontrolled disease that willinterfere with the conduct of this study or the assessment of safety and efficacy ofthe 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 tothe Screening Visit.

9. Subjects have a known hypersensitivity to sulfonamides, dibenzazepine derivatives, ortricyclic antidepressants.

10. Subjects have a history of bone marrow depression, low platelet count or other blooddyscrasia.

11. Subjects have a history of acute intermittent porphyria.

12. Subjects have a history of renal disorder (serum creatinine level of > 135 ìmol / l (1.5 mg/dL at the Screening Visit), hepatic disorder or clinically significantabnormal liver function tests; aspartate aminotransferase (AST) and alanineaminotransferase (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 squamouscell carcinoma).

15. Subjects have a history of psychiatric illness or mood disorder requiringelectro-convulsive or drug therapy within the previous 6 months which is considereduncontrolled; a history of suicide attempt; alcohol or drug abuse; chronic treatmentwith benzodiazepines or barbiturates.

16. Subjects are currently taking carbonic anhydrase inhibitors.

17. Subjects have a history of pancreatitis, nephrolithiasis or hypercalcuria, clinicallysignificant laboratory or electro-cardiographic abnormalities, or uncontrolledhypertension.

18. Subjects are currently taking mono-amine oxidase inhibitors (MAOIs) or any otherexcluded medications.