A multicentre, randomised, active comparator, parallel group study to compare the effect on cognition of adjunctive therapy with zonisamide versus sodium valproate. - COGZ

Active, not recruiting

• Conditions: Refractory partial seizures, with or without secondary generalisation.; MedDRA version: 9.1Level: LLTClassification code 10065336Term: Partial epilepsy

• Registration Number: EUCTR2007-005313-19-NL
• Lead Sponsor: Eisai Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-29
• Last Update Posted: 21 August 2012

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Adult subjects with a clinical diagnosis of idiopathic/cryptogenic/non-progressive symptomatic localisation-related epilepsy, with partial onset seizures with or without secondary generalisation, who are receiving fixed dose carbamazepine monotherapy Subjects must require addition of another anti-epileptic drug (AED) to their anti-epileptic therapy.

1. Subjects with a clinical diagnosis of idiopathic/cryptogenic/non progressive symptomatic localisation-related epilepsy with partial onset seizures with or without secondary generalisation according to International League Against Epilepsy (ILAE) classification27. Diagnosis should be clinically established by history, by previous electroencephalogram (EEG) and by previous magnetic resonance imaging or computer tomography of the brain, consistent with localisation related epilepsy. No lower or upper limit of baseline seizures is defined.
2. Able and willing to sign informed consent form (ICF) in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines.
3. Male or female subjects aged =18 years.
4. Subjects taking carbamazepine as monotherapy at baseline. Dose of carbamazepine is within that recommended by the SPC. Carbamazepine dose has not been altered during the previous 2 weeks prior to the start of the Baseline Period, or 6 weeks if the Baseline Period is to be shortened due to the availability of a retrospective seizure history. The carbamazepine dose is to remain stable throughout the study.
5. Subjects requiring addition of another AED.
6. Female subjects of childbearing potential must not be pregnant (as confirmed by negative serum beta-human chorionic gonadotropin (ßHCG) at screening and negative urine pregnancy test at baseline and during the study), must not be lactating and must use a medically acceptable form of contraception during the study and for at least 1 month after discontinuation of study drug.
Medically acceptable contraception is defined here as:
High dose combined oral contraceptive (OC) pill (50µg of oestrogen preparation) Documented surgical sterilisation or documented vasectomised sexual partner Intrauterine device in place for at least 3 months and not exceeding the documented replacement date. (If the replacement date is not available, the device must not have been in situ for more than 5 years).
Women more than 2 years post-menopause
Abstinence
Examples of contraception NOT acceptable include, but are not limited to: Conventional dose of combined OC (<50µg oestrogen)
Progesterone-only OC
Contraceptive implant
Contraceptive patch
Progesterone injection
Barrier contraception: - Condom
- Diaphragm
- Sponge
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Previous treatment with valproate (> 4 weeks usage) or previous treatment with zonisamide.
2. Use of an AED other than carbamazepine less than 6 weeks prior to randomisation, and other than carbamazepine, zonisamide or sodium valproate during the study.
3. Hypersensitivity to zonisamide or valproate or their respective excipients.
4. Predisposing condition potentially altering the absorption, distribution or elimination of zonisamide or valproate.
5. Sulphonamide allergy.
6. Subjects with diagnosed idiopathic/primary generalised epilepsy or with results of clinical investigations or EEG that suggest idiopathic/primary generalised epilepsy.
7. History of status epilepticus within 12 months of screening whilst complying with AED therapy.
8. History of cluster seizures.
9. History of non epileptic seizures.
10. Use of benzodiazepines (use as rescue medication on up to 3 occasions in the study is permitted)
11. Regular treatment with antihistamines.
12. Use of ketogenic diet.
13. Use of acetozolamide or other carbonic anhydrase inhibitors triamterene, vitamin C (>2g/day), regular antacids or other medicines associated with nephrolithiasis and medicinal products with anticholinergic activity less than one month prior to randomisation or during the study.
14. Subjects with a functioning vagal nerve stimulator implanted, or due to be implanted within the expected duration of the study.
15. Subjects expected to undergo any surgery within the expected duration of the study.
16. History of renal calculi or renal insufficiency (above a creatinine level of 194 mmol/L; 1.5mg/dL
17. Active psychiatric disease (minor depression which is controlled by anti-depressant medication is permitted)
18. History of suicide attempt within last 2 years.
19. History of drug or alcohol abuse within the last 2 years.
20. History of cerebrovascular disease/stroke or transient ischemic attacks.
21. Progressive neurological disease (as determined by pre- existing brain imaging such as CT or MRI performed maximally 5 years before the screening visit)
22. Previous or current brain neoplasm
23. Behavioral disturbances that may impair the subject’s ability to complete the neuropsychological tests.
24. Subjects with clinically significant active hepatic disease, cardiovascular, haematological, metabolic, respiratory, renal, endocrinological and gastrointestinal diseases or any other clinically significant organic disease, within 30 days prior to the Screening Visit.
25. Neoplastic disease within the last 5 years except non-metastatic and adequately treated cutaneous squamous cell carcinoma.
26. Diagnosis of human immunodeficiency virus (HIV) or Hepatitis B or C.
27. Female subjects who are lactating, pregnant or intending to become pregnant. 28. Subjects with history of demonstrated non compliance with medication or an inability to maintain a seizure diary.
29. Subjects considered by the Investigator not to be within normal cognitive limits. 30. Participation in clinical study within 30 days of screening.
31. Clinically significant laboratory value abnormalities at baseline (including alanine aminotransferase and aspartate aminotransferase values > 3 x upper limit of normal value).
32. Weight <40kg.
33. Personal or family history of severe hepatic dysfunction.
34. Subject has porphyria.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified