E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with newly diagnosed partial-onset seizures |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
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 demonstrate that monotherapy with Eslicarbazepine Acetate (ESL; 800 to 1600 mg once daily) is not inferior to monotherapy with controlled-release carbamazepine (CBZ-CR; 200 to 600 mg twice daily) in adults (≥18 years) with newly diagnosed epilepsy experiencing partial-onset seizures. |
|
E.2.2 | Secondary objectives of the trial |
To further demonstrate the efficacy, safety, and pharmacokinetics of ESL in this patient population at the doses used. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Visit 1 (Days –1 to –7): 1. Have signed an informed consent before undergoing any study-related activities. Subjects of Asian ancestry are required to give written informed consent for genotyping. 2. Male or female ≥18 years of age. 3. Newly diagnosed epilepsy with at least 2 well documented, unprovoked, clinically evaluated and classified partial seizures (with or without secondary generalization) with clear focal origin, documented clinically by electroencephalogram (EEG) or imaging studies, within 12 months of Visit 1. 4. At least 1 seizure during the previous 3 months. 5. Demonstrated cooperation and willingness to complete all aspects of the study. 6. Female subjects without childbearing potential (2 years postmenopausal, bilateral oophorectomy or tubal ligation, or complete hysterectomy) are eligible. Female subjects with childbearing potential must not be pregnant as confirmed by a negative serum beta-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal, double-barrier contraception method for the duration of the study and until the Post-study visit (PSV).
Visit A1, Day 1 (randomization and start of double-blind treatment period): 7. Have satisfactorily completed the electronic subject diary (eDiary). 8. Female subjects with childbearing potential must not be pregnant as confirmed by a negative urine pregnancy test and sexually active females must be using a medically acceptable effective non-hormonal, double-barrier contraception method for the duration of the study and until the PSV.
|
|
E.4 | Principal exclusion criteria |
Visit 1 (Days –1 to –7): 1. History of pseudo-seizures. 2. Seizures occurring only in clusters. 3. Subjects with a history of absence, myoclonic, clonic, tonic or atonic seizures. 4. Documented EEG within 12 months of Visit 1 suggestive of primarily generalized epilepsy. 5. History of status epilepticus within the 3 months prior to Visit 1. 6. Known progressive neurologic disorder (progressive brain disease, epilepsy secondary to progressive cerebral lesion) as assessed by magnetic resonance imaging or computer tomography. 7. History of schizophrenia or suicide attempt. 8. Former or current use of any AED, except for the use of a single AED for a maximum duration of 2 weeks before Visit 1. 9. Previous use of ESL or CBZ. 10. Using mono-amine oxidase inhibitors (MAOIs), tricyclic antidepressants, nefazodone, or isoniazid. 11. Known hypersensitivity to carboxamide derivatives or tricyclic antidepressants. 12. History of alcohol, drug, or medication abuse within the last 2 years. 13. Uncontrolled cardiac (including atrioventricular block and other clinically significant electrocardiographic abnormalities), renal, hepatic, endocrine, gastrointestinal, metabolic, hematological, or oncology disorder. 14. History of bone marrow depression. 15. History of hepatic porphyrias (e.g. acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). 16. Relevant clinical laboratory abnormalities (e.g. sodium <130 mmol/L, alanine or aspartate transaminases >2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (measured at Visit 1). 17. Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m2 (measured at Visit 1). 18. Subjects of Asian ancestry who test positive for the presence of the HLA-B*1502 allele. 19. Pregnancy or lactating. 20. Participation in other drug clinical trial within the last 2 months or having received an IMP within 5 half-lives of that IMP, whichever is longer. 21. Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject’s ability to comply with the study protocol.
Visit A1, Day 1 (randomization and start of double-blind treatment period): 22. Former or current use of any AED, except for the use of a single AED for a maximum duration of 2 weeks before Visit 1 and with a drug-free period of at least 5 days before Visit A1. Benzodiazepines are allowed, no more than twice a week, for an epileptic indication and as rescue medication during the ≥5-day drug-free period. 23. Using MAOIs, tricyclic antidepressants, nefazodone, or isoniazid. 24. Pregnancy. 25. Any other condition or circumstance that, in the opinion of the investigator, could compromise the subject’s ability to comply with the study protocol.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects in the per protocol set who are seizure free for the entire 26-week Evaluation Period at the last received dose level. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 102 |
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
|
The end of the study is triggered by the date of the last visit for the last subject who completes the 26-week Evaluation Period. When the timing is known for the last subject to attend their End-of-Evaluation Period visit (Visit A4, B4, or C4), all centers will be instructed to contact all subjects and schedule this last Extension Phase Visit. |
|
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |