E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
simple partial seizures with no motor symptomatology Epilepsy |
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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 |
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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 Eslicarbazepine acetate QD at doses of 800 mg and 1200 mg compared with placebo as adjunctive therapy in patients with refractory partial epilepsy over a 12-week maintenance period. |
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E.2.2 | Secondary objectives of the trial |
(1) To evaluate the safety and tolerability of Eslicarbazepine acetate at QD doses of 800 mg and 1200 mg in comparison with placebo, over a 12-week maintenance period preceded by a 2-week titration period. (2) To evaluate the safety and tolerability of Eslicarbazepine acetate at doses titrated to an efficacy or safety endpoint over a 1-year open-label period. (3) To assess the maintenance of therapeutic effects of Eslicarbazepine acetate over a 12-week maintenance period preceded by a 2-week titration period, and over a 1-year open-label period. (4) To assess the drug-drug pharmacokinetic (PK) interactions between Eslicarbazepine acetate and concomitant anti-epileptic drugs (AEDs) over the double-blind and open-label parts of the study. (5) To assess the health-related quality-of-life and depressive symptoms over the doubleblind and open-label parts of the study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-At visit 1 (screening), patient must be/have: *written informed consent signed by patient *Aged 18 years or more; *Documented diagnosis of epilepsy for at least 12 months prior to screening *At least 4 partial-onset seizures (including subtypes of simple partial, complex partial and/or partial seizures evolving to secondarily generalised) on the 4-weeks prior to screening *Currently treated with 1 or 2 AEDs (any except oxcarbazepine), in a stable dose regimen during at least 1 month prior to screening (patients using vigabatrin should have been on this medication for at least 1 year with no deficit in visual field identified, and a confirmatory test should be available within 1 month before study entry *If present, vagus nerve stimulation [VNS] is considered an AED, i.e., only up to 1 concomitant AED is allowed in patients with VNS); excepting epilepsy, patient is judged to be in general good health based on medical history, physical examination (PE) and clinical laboratory tests *Post-menopausal women or female patients otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; in case of woman of childbearing potential (WOCBP), patient must present a serum β-human chorionic gonadotropin (β-hCG) test consistent with a non-gravid state and agree to remain abstinent or use reliable contraception (hormonal contraception should be combined with a barrier method) beginning at screening and continuing at least to the post-study visit. -At visit 2 (randomisation), patient must have *At least 4 partial-onset seizures per 4 weeks during the 8-week baseline period prior to randomisation (documented in a diary) and no seizure-free interval exceeding 21 consecutive days *In case of WOCBP, patient must present a urine β-hCG test consistent with a non-gravid state; diaries satisfactorily completed by the patient or his/her caregiver *Satisfactorily complied with the study requirements during the baseline period. |
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E.4 | Principal exclusion criteria |
-At visit 1 (screening), patients must not be / have: *Only simple partial seizures with no motor symptomatology (classified as A2-4 according to the International Classification of Epileptic Seizures) *Primarily generalised seizures *Known progressive neurological disorders (progressive brain disease, epilepsy secondary to progressive cerebral lesion) *Occurrence of seizures too close to count accurately *History of status epilepticus or cluster seizures (i.e., 3 or more seizures within 30 minutes) within the 3 months prior to screening *Seizures of nonepileptic origin *Major psychiatric disorders; seizures of psychogenic origin within the last 2 years *History of schizophrenia or suicide attempt; currently treated with oxcarbazepine *Using benzodiazepines on more than on an occasional basis (except when used chronically as AED) *Previous use of Eslicarbazepine acetate or participation in a clinical study with Eslicarbazepine acetate *Known hypersensitivity to carbamate derivatives; history of abuse of alcohol, drugs or medications within the last 2 years *Uncontrolled cardiac, renal, hepatic, endocrine, gastrointestinal, metabolic, haematological or oncology disorder *Second or third-degree atrioventricular blockade not corrected with a pacemaker *Relevant clinical laboratoryabnormalities (e.g., Na+ <130 mmol/L, alanine or aspartate transaminases [ALT or AST] >2.0 times the upper limit of the normal [ULN], white blood cell count [WBC] <3,000 cells/mm3) Estimated creatinine clearance (CLCR) <60 mL/min; pregnancy or nursing *Participation in other drug clinical trial within the last 2 months or received an investigational drug within 5 half-lives of this other product, whichever is longer *Not ensured capability to perform the trial; any other condition or circumstance that, in the opinion of the investigator, may compromise the patient’s ability to comply with the study protocol. -At visit 2 (randomisation), patients must not be / have: *Inadequate compliance to concomitant AEDs during the 8-week baseline period *Inadequate completion of the study diary *Any other condition or circumstance that, in the opinion of the investigator, may compromise the patient’s ability to comply with the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change of seizure frequency over the 12-week maintenance period as compared with the 8-week baseline period. Seizure frequency for all the periods considered, including the maintenance and baseline periods, will be standardised to a “frequency per 4 weeks” basis. |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |