| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065336 |
| E.1.2 | Term | Partial epilepsy |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the efficacy of zonisamide in paediatric epilepsy subjects with partial onset seizures treated with one or two other AEDs. |
|
| E.2.2 | Secondary objectives of the trial |
To further explore the efficacy and safety of zonisamide.
To explore the effect of zonisamide on cognition, and growth and development. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is male or female aged 6–17 years inclusive.
2. Parent/guardian is willing to sign an approved informed consent form, and accompany the subject on all study visits.
3. Subject is willing to give informed (written or verbal) assent and if appropriate written informed consent.
4. Subject has a clinical diagnosis of epilepsy with partial-onset seizures with or without secondary generalised seizures according to the International League Against Epilepsy’s Classification of Epileptic Seizures (1981).
5. Diagnosis has been established by clinical history, electroencephalogram (EEG) and computed tomography/ magnetic resonance imaging (CT/MRI) of the brain consistent with localisation related epilepsy.
6. Subject has >= four (simple or complex) partial seizures (with or without secondary generalisation) per month over the eight week Baseline Period (comprising four-week routinely collected seizure data and four-week Screening Period data) with at least one seizure in each four week period and with no 21 day period being seizure free.
7. Subject is taking a stable regimen of one or two other AEDs for at least two months prior to Visit 1 (start of the Screening Period).
NOTE: If using a vagal nerve stimulator (VNS), it must have been implanted for at least five months and stimulator parameters must remain unchanged for at least two months prior to Visit 1 (start of the Screening Period), and throughout the entire study period. VNS will be considered as one AED for the purposes of this study.
8. Subject is in general good health as determined by medical history, physical exam and screening laboratory results.
9. Parent/guardian is willing and able to complete a seizure diary for the duration of the study. |
|
| E.4 | Principal exclusion criteria |
1. Subject of body weight < 20 kg at the Screening Visit.
2. Subject is unable to swallow capsules.
3. Subject has progressive neurological disease (determined by diagnosis or a pre-existing brain image such as a CT scan or MRI).
4. Subject has a history of idiopathic generalised epilepsy as defined by the International League Against Epilepsy (ILAE).
5. Subjects with Lennox-Gastaut syndrome, absence, myoclonic, clonic and/or tonic (other than secondary generalised) and atonic seizures.
6. Subject has psychogenic seizures
7. Subject has a history of status epilepticus within a year of the Screening Visit whilst taking AEDs.
8. Subject has seizures that only occur in clustered patterns, or has seizures that are too close together to count accurately.
9. Subject has a history of renal calculi or renal insufficiency (creatinine levels >135 μmol/l (1.5mg/dl).
10. Subject had a predisposing condition that might interfere with absorption, distribution, or excretion of zonisamide.
11. Subject has a history of psychiatric illness.
12. Subject has a history of suicide attempt.
13. Female subject who is pregnant or lactating.
14. Subject has a history of demonstrated non-compliance with treatment or, the subject, parent or legal guardian can be reasonably expected not to be compliant with study procedures or to complete the study.
15. Female subject of 10 years of age or greater or of child bearing potential (i.e. started menses) and is not taking or prepared to take a medically acceptable form of contraception (i.e. oral contraceptive pill, surgical sterlisation, an implant or an injected form of contraception, or intrauterine device), or who is not prepared to abstain from sexual activity for the duration of the study and one month after last administration of study medication.
NOTE: Should a female subject become of childbearing potential during the study, they must be reconsented in order to give consent to undergo pregnancy testing and either confirm abstinence or receive medically appropriate form of contraception.
16. Subject has clinically significant abnormal laboratory values at the Screening Visit.
17. Subject has received previous treatment with zonisamide.
18. Subject is treated with a ketogenic diet or is likely to have surgery for epilepsy in the trial period.
19. Subject requires frequent rescue benzodiazepines (> once a week).
20. Concomitant use of felbamate or use of felbamate within 3 months prior to Visit 1.
21. Subject has elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN).
22. Subject has evidence of significant active and unstable haematological disease; i.e. white blood cell (WBC) count < 2500/μL or an absolute neutrophil count < 1000/μL
23. Subject with clinically significant active hepatic disease, cardiovascular, metabolic, respiratory, renal, endocrinological and gastrointestinal diseases or any other clinically significant organic disease, within 60 days prior to the Screening Visit.
24. Subjects with known or suspected history of alcoholism or drug abuse within the previous two years, or a positive finding on urinary drug screening of any drugs other than prescribed medications.
25. Subjects with any other condition that would make them, in the opinion of the Investigator unsuitable for this study.
26. Subjects who have participated in a clinical trial involving administration of an investigational compound (including zonisamide) within three months of the Screening Visit.
27. Subjects with a known or suspected hypersensitivity to zonisamide, sulphonamides or to any of the excipients of the investigational product.
28. Subjects taking acetazolamide, any carbonic anhydrase inhibitors e.g. topiramate, furosemide and any drugs with anticholinergic activity.
29. Subjects who do not have a complete seizure diary during the Screening Period.
30. Subjects with active and/or insufficiently treated neurocysticercosis or intracranial tuberculosis. Note: subjects who have completed a curative antihelminthic or antituberculous treatment course more than 3 months before screening and who are free of signs and symptoms of active infection (including on a post-treatment CT/MRI scan), may be enrolled in the study.
31. Subjects taking anti-psychotics, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and benzodiazepines with barbiturates and amphetamines for diseases other than epilepsy within three months of screening.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of responders in the Maintenance Period A. A responder is defined as a subject with a decrease from baseline in seizure frequency of >= 50%. The primary analysis will assess the proportion of responders in the stable dose period (i.e. 28 day seizure frequency in the Week 8 to 20 compared to Week -8 to 0). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Refer to Section 7.2 in protocol:
The start and end of the study at the study site are defined as the first visit to the study centre by a potential subject for screening, and the end of the study is defined as the last visit by any randomised subject. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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