|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|E.1.2 Medical condition or disease under investigation
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To compare the effect of add-on treatment with zonisamide to that of placebo on cognition and sedation in an elderly population with refractory partial seizures.
|Secondary objectives of the trial
|To assess the safety and tolerability of add-on zonisamide in elderly patients. To assess the effect of zonisamide on cognition: ABNAS scale. To explore the efficacy of add-on zonisamide in elderly patients
|Trial contains a sub-study
|Principal inclusion criteria
|1. Male or female patients aged 65 years or over.
2. Patients able and willing to give written informed consent in accordance with ICH GCP guidelines.
3. Patients who are reliable and willing to make themselves available for visits to the Investigator site and study telephone calls.
4. Patients capable of maintaining a seizure daily diary or who have access to a caregiver who is prepared to complete this on the patient’s behalf.
5. Patients able to complete the questionnaires used in this study.
6. Patients with localisation related epilepsy, with simple and/or complex partial seizures with or without secondary generalised seizures as defined by the International League Against Epilepsy (ILAE) criteria.
7. Patients who have at least one well documented seizure in the four weeks preceding the Randomisation Visit (Visit 2) and are deemed to require additional AED medication.
8. Patients will be receiving at least one, but not more than two other marketed AEDs as concomitant medication, and the dosage should be stable for at least four weeks before the Screening Visit.
|Principal exclusion criteria
|1. Patients with seizures attributed to metabolic causes (e.g. electrolyte disturbances, hyperglycaemia).
2. Patients with seizures which could be attributed to use of a drug.
3. Presence of primary generalised epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
4. Patients with a history of eating disorders or a body weight below 40 kg.
5. Patients with a history of blood dyscrasias.
6. Patients with a history of renal stones or having risk factors for nephrolithiasis such as a family history of nephrolithiasis or hypercalciuria.
7. Patients with an increased risk factor for rhabdomyolysis such as uncontrolled hypothyroidism, personal or family history of muscle disorders.
8. Patients taking concomitant medication associated with nephrolithiasis and medications increasing the risk of rhabdomyolysis.
9. Patients taking rifampicin or drugs with anticholinergic effects.
10. Patients taking carbonic anhydrase inhibitors or topiramate.
11. Patients with a history of pancreatitis.
12. Patients with a history of Stevens Johnson Syndrome.
13. Patients with elevated levels of serum creatinine >165 micromol and/or severe hepatic impairment to the extent that the protocol dose titration schedule cannot be followed.
14. Patients suffering from clinically significant psychiatric illness, psychological or behavioural problems (e.g. major depressive or bipolar disorder, psychotic disorders, delirium or incapacitating anxiety disorders) or other disorders, which could interfere with study participation.
15. Patients with a history (within the last 12 months) of alcohol or drug abuse or dependency.
16. Patients with hypersensitivity to zonisamide, to any of the excipients or to sulphonamides.
17. Patients considered by the Investigator to be an unsuitable candidate for receiving zonisamide or considered unlikely to comply with the protocol.
18. Any patient who has a contraindication for zonisamide treatment.
19. Treatment with any investigational product/drug 30 days prior to the Screening Visit.
|E.5 End points
|Primary end point(s)
|The primary objective of this study is to compare the effect of zonisamide to that of placebo, as add-on treatment, on cognition and sedation in the elderly population with refractory partial seizures. The primary parameter to assess cognition is the CVST task of the FePsy. The primary parameter to assess sedation is the Bond-Lader mood rating scale. The primary variables will be analysed in the Per Protocol population, and as a secondary analysis, additionally in the ITT population
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
| Information not present in EudraCT
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The end of the study is defined as database lock, as access to site information (for query resolution) is required following last patient last visit (LPLV) until database lock.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days