Official Title: “A Randomized, Multi-Centre, Double-Blind Study, to Compare the Efficacy and Safety of Zonisamide and Carbamazepine as Monotherapy, in Newly Diagnosed Partial Epilepsy”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

Intervention(s) in this Clinical Trial

• Drug: Zonisamide
  • 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.
• Drug: Carbamazepine
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• Active Comparator: 2

Primary Measures

• The proportion of subjects remaining seizure free for at least a 26 week period when treated with zonisamide or carbamazepine.
  • Time Frame: 26 weeks
    Safety Issue?: Yes

Secondary Measures

• Proportion of subjects seizure free for 52 weeks. Incidence of AEs, SAEs, withdrawals, out-of-normal-range laboratory values, abnormal 12-lead ECG; physical examination findings; ABNAS (Aldenkamp-Baker Neurotoxicity Scale); Bond-Lader Scale; QOL.
  • Time Frame: 52 weeks
    Safety Issue?: Yes

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 ìmol / 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eisai Limited

Overall Clinical Trial Officials and Contacts

Robert van Maanen, MD Study Director Eisai Limited  

Overall Contact: Eisai Ltd. 0208 600 1400 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00477295

Study ID Number: E2090-E044-310

ClinicalTrials.gov Identifier: NCT00477295

Health Authority: European Union: European Medicines Agency