Estudio multicentro, aleatorizado, de comparador activo y grupos paralelos para comparar el efecto sobre la cognición de la terapia adyuvante con zonisamida frente al valproato sódico. - COGZ
- Conditions
- Terapia concomitante en el tratamiento de pacientes adultos con crisis parciales, con o sin generalización secundaria.MedDRA version: 9.1 Level: LLT Classification code 10065336 Term: Partial epilepsy
- Registration Number
- EUCTR2007-005313-19-ES
- Lead Sponsor
- Eisai Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
Adult subjects with a clinical diagnosis of non-symptomatic (i.e., idiopathic or cryptogenic) localisation-related epilepsy, with partial onset seizures with or without secondary generalisation, who are receiving fixed dose carbamazepine monotherapy or can be transferred to carbamazepine monotherapy in the two months before the study baseline. Subjects must require addition of another anti-epileptic drug (AED) to their anti-epileptic therapy, either because they continue to have seizures (are refractory), or because they wish to switch to another AED for other reasons (e.g. tolerability).
1. Subjects with a clinical diagnosis of non-symptomatic (i.e., idiopathic or cryptogenic) 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 or who can be transferred to carbamazepine monotherapy in the two months before the Screening Visit. 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, either because they continue to have seizures (are refractory), or because they wish eventually to switch to another AED for other reasons after the study completion (e.g. tolerability reasons).
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
1. Previous treatment with valproate or 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 during the Baseline Period or during randomised treatment.
11. Regular treatment with antihistamines.
12. Use of ketogenic diet.
13. Use of acetozolamide, triamterene, vitamin C (>2g/day), regular antacids or other medicines associated with nephrolithiasis less than one month prior to randomisation or during the study.
14. Subjects with a 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 the upper normal limits of creatinine).
17. Active psychiatric disease.
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; progressive neurological disease; focal central nervous system pathology or behavioural disturbances that may impair the subject’s ability to complete the neuropsychological tests; or previous or current brain neoplasm.
21. Neoplastic disease within the last 5 years except non-metastatic and adequately treated cutaneous squamous cell carcinoma.
22. Diagnosis of human immunodeficiency virus (HIV) or Hepatitis B or C.
23. Other clinically significant organic disease.
24. Female subjects who are lactating, pregnant or intending to become pregnant.
25. Subjects with history of demonstrated non compliance with medication or an inability to maintain a seizure diary.
26. Subjects considered by the Investigator not to be within normal cognitive limits.
27. Participation in clinical study within 30 days of screening.
28. Clinically significant laboratory value abnormalities at baseline.
29. Weight <40kg.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effects of zonisamide on cognition, when administered as adjunctive treatment to adults with refractory partial epilepsy taking fixed dose carbamazepine monotherapy, in comparison with adjunctive sodium valproate. ;<br> Secondary Objective: To assess efficacy as measured by the percentage change and 50% response rate in 28-day seizure frequency from Baseline to Week 12.<br> To assess safety as measured by the incidence of AEs and SAEs; incidence of withdrawal for TEAEs; physical and neurological examinations; vital signs; routine clinical laboratory tests; and weight.<br> ;Primary end point(s): The change from baseline to Week 12 in the Computerised Visual Searching Task Reaction Time (CVST) from the Ferum Psyche (FePsy) cognitive battery, which measures central information processing speed.
- Secondary Outcome Measures
Name Time Method