E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with recently diagnosed partial-onset seizures |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients with recently diagnosed partial epilepsy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
E.1.2 | System Organ Class | 100000004852 |
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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 confirm maintenance of efficacy of eslicarbazepine acetate (ESL, 800 mg to 1600 mg once daily [QD]) monotherapy during long-term treatment in adults (≥18 years) with recently diagnosed epilepsy experiencing partial-onset seizures. |
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E.2.2 | Secondary objectives of the trial |
1. To further demonstrate the efficacy of ESL in subjects switching from carbamazepine controlled-release (CBZ-CR) treatment.
2. To demonstrate the safety of ESL in subjects switching from CBZ-CR treatment and in subjects already treated with ESL monotherapy for at least one year (i.e. during long-term treatment).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion in the extension study, subjects must fulfill all of the following at Visit 1 (Day 1, start of the open-label extension study):
1. Participated in the preceding double-blind study and were still ongoing at the time of unblinding.
2. Have signed informed consent before undergoing any activities related to the open-label extension study.
3. Demonstrated cooperation and willingness to complete all aspects of the study.
4. 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 ß-human chorionic gonadotropin (hCG) test and sexually active females must be using a medically acceptable effective non-hormonal method of contraception for the duration of the study and until the Post-study Visit (PSV). |
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E.4 | Principal exclusion criteria |
Subjects having any of the following at Visit 1 are to be excluded from the study:
1. Excluded from the double-blind study due to seizure in the Maintenance or Extension Phase, or at dose level C (either CBZ-CR or ESL), or discontinued prematurely due to any other reason in the double-blind study.
2. Presence of any major protocol violation during the double-blind study which may have an impact on the compliance during this extension study.
3. Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (C-SSRS).
4. Occurrence of an adverse event (AE) indicating a suspected presence of atrioventricular block (2nd degree and above) or of any other AEs during the double-blind study which are judged by the investigator as contraindicative to further participation in the open-label extension study.
5. Events of alcohol, drug, or medication abuse during the preceding double-blind study.
6. Relevant clinical laboratory abnormalities (e.g. sodium <125 mmol/L, alanine or aspartate transaminases >2 x the upper limit of normal, white blood cell count <3000 cells/mm3) (as reported at Visit 1).
7. Pregnancy or lactating.
8. Any oth r condition or circumstance that, in the opinion of the investigator, could compromise the subject’s ability to comply with the extension-study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to treatment failure, defined as time from start of open-label ESL treatment at Visit 1 until withdrawal due to AE or due to lack of efficacy (i.e. inadequate seizure control). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Treatment retention time (overall, i.e. including previously CBZ-CR treated subjects, and by reason) at the last evaluated dose during open-label treatment, where treatment retention time is defined as the time from start of the extension study until withdrawal of ESL due to AEs or due to lack of efficacy (i.e. inadequate seizure control).
• Time to withdrawal for any reason at the last evaluated dose.
• Changes in quality of life assessed using the QOLIE-31.
• Changes in overall treatment satisfaction as assessed on a 4-point scale.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
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 | No |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Chile |
Croatia |
Czech Republic |
Estonia |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Latvia |
Lithuania |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Ukraine |
United Kingdom |
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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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The complete study duration including treatment with ESL under open-label conditions and follow-up is expected to last approximately 2 years (105 weeks).
In case ESL as monotherapy will achieve MA prior to the end of 2017, the study may be discontinued prematurely within 42 days after achievement of MA.
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |