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 | 10015037 |
E.1.2 | Term | 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 evaluate the efficacy of zonisamide compared with carbamazepine administered as monotherapy to subjects with newly diagnosed partial epilepsy, by evaluating the level of absence of epileptic seizures for 26 weeks. |
|
E.2.2 | Secondary objectives of the trial |
To further explore the efficacy of zonisamide compared with carbemazepine.To evaluate the safety of zonisamide compared with carbamazepine.To evaluate quality of life (QoL) of subjects who take zonisamide compared with those who take carbamazepine. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Men and women aged between 18 - 75 inclusive. 2. Subjects with newly diagnosed untreated epilepsy who have experienced at least two documented, unprovoked seizures, evaluated clinically and classified as partial epileptic seizures (with or without secondary generalisation) or generalised tonic-clonic seizures (without a clear focal origin) in the 12 months preceding the Screening visit, with at least one in the 3 months preceding the Screening visit. (more than one seizure in a 24 hour period will be considered as a single seizure). 3. Subjects must not have previously used antiepileptic drugs (AED) or have received treatment with an AED for a maximum duration of two weeks before the Randomisation visit (T1). 4. Subjects with a documented electroencephalogram (EEG) carried out within the 12 months preceding the Screening visit, compatible with localisation-related epilepsy (to exclude primary generalised epilepsy). 5. Subjects with a documented computerised axial tomography (CAT) or a magnetic resonance (MR) scan which confirms the absence of a progressive neurological lesion, carried out within the 12 months preceding the Screening visit. 6. Women who are not of child-bearing age (postmenopausal for two years, women who have undergone a bilateral oophorectomy or tubal ligature, complete hysterectomy) are eligible. Women of child-bearing age must not be pregnant, as confirmed by a negative pregnancy test during screening and randomisation, must not be breast-feeding and must use a medically acceptable contraceptive method for the duration of the study and for one month after having stopped taking the study drug. Medically acceptable contraceptive methods are defined at this time as oral birth control pills containing at least 50 micrograms of ethynilestradiol for ingestion, contraceptive injections and implants or intrauterine devices implanted for at least three months. 7. Subjects who are able and willing to follow the procedures planned by the study, keep a diary for epileptic seizures and report any AEs. 8. Subjects who are able and willing to provide written informed consent. |
|
E.4 | Principal exclusion criteria |
1. Subjects with a past history of clinical examinations, including ECG data suggesting idiopathic generalised epilepsy according to the definition of the International League Against Epilepsy (ILAE). 2. Subjects with a past history of epileptic seizures not of a myoclonic, clonic, tonic or atonic nature. 3. Subjects with a past history of epileptic conditions or non epileptic seizures (for example, metabolic, pseudo-epileptic seizures). 4. Subjects with seizures related to narcotics, alcohol, acute diseases, mental retardation or subjects with seizures related to stressful situations. 5. Subjects with progressive encephalopathy or results indicative of progressive CNS (central nervous system) diseases or lesions (for example infections, demyelinisation or tumours). 6. Subjects with a past history of significant or currently uncontrolled pathologies which would interfere with the conduct of the study or the evaluation of the safety and efficacy of the study drug. 7. Subjects previously treated with carbamazaepine or zonisamide. 8. Subjects who have received a trial drug or device in the three months preceding the Screening visit. 9. Subjects with known hypersensitivity to sulfonamides, dibenzazepine derivatives or tricyclic antidepressive drugs. 10. Subjects with a past history of marrow depression, reduced platelet count or other forms of blood dyscrasia. 11. Subjects with a history of acute intermittent porphyria. 12. Subjects with a past history of renal disorders (serum levels of creatinine >135 mol/l (1.5 mg/dl) at the Screening visit), liver disorders or clinically significant abnormalities in liver function tests; aspartate aminotransferases (AST) and alanine aminotransferases (ALT) >2 times the upper limit of normal ranges. 13. Subjects with a body weight below 40 kg. 14. Subjects with a past history of malignant progressive neoplasia in the preceding 5 years (with the exclusion of a past history of suitably treated non metastatic skin squamocellular carcinoma). 15. Subjects with a past history of psychiatric diseases or mood disorders requiring electroconvulsive or pharmacological therapy in the preceding 6 months and considered to be uncontrolled; past history of suicide attempts, alcohol or narcotic abuse; chronic treatment with benzodiazepine or barbiturates. 16. Subjects who are currently taking carbonic anhydrase inhibitors. 17. Subjects with a past history of pancreatitis, nephrolithiasis or hypercalciuria, clinically significant abnormalities in laboratory tests or on electrocardiographs or uncontrolled hypertension. 18. Subjects who are currently taking monoamine oxidase inhibitors (MAOIs) or other permitted drugs. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects remaining sizure free for at least a 26 week period when treated with zonisamide or carbamazepine. A subject will be classified as having achieved a 26 week seizure free period if they are free of all seizures, regardless of zeizure type, for 26 weeks when on stable dose of carbamazepine or zonisamide |
|
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |