E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 monotherapy at a dose of 1600 mg/day in subjects with partial epilepsy not well controlled by current antiepileptic drugs (AED), in comparison to a historical pseudo-placebo control group in accordance with the White Paper on Alternative Monotherapy Design in the Treatment of Epilepsy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of eslicarbazepine acetate monotherapy at a dose of 1200 mg/day in subjects with partial epilepsy not well controlled by current AEDs.
To evaluate the safety of eslicarbazepine acetate monotherapy in subjects with partial epilepsy not well controlled by current AEDs.
To evaluate the population pharmacokinetics (PK) of eslicarbazepine acetate monotherapy subjects with partial epilepsy not well controlled by current AEDs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Diagnosis of partial epilepsy as defined in the Classification of Seizures of the International League Against Epilepsy (ILAE)23 (simple partial seizures with observable motor component, or complex, with or without secondary generalization)
a.Medical history of seizures;
b.Absence of confounding factors (pseudoseizures, syncope);
c.Documented EEG recording (done within 10 years prior to screening) consistent with focal onset epilepsy.
2.Documented CT or MRI scan conducted within 10 years prior to screening, showing the absence of a progressive structural abnormality (eg, tumor). Mesial temporal sclerosis is acceptable.
3.≥4 partial onset seizures during the 8 weeks prior screening with no 28-day seizure free period.
4.Stable treatment with 1-2 AEDs during the last 4 weeks prior to screening.
General:Subjects are male or female and aged 18-70 years, inclusive. |
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E.4 | Principal exclusion criteria |
1.Subjects with only simple partial seizures without a motor component.
2.Presence of generalized seizure syndromes (eg, juvenile myoclonic epilepsy or Lennox-Gastaut syndrome).
3.History of pseudo-seizures.
4.Current seizures related to an acute medical illness.
5.Seizures secondary to metabolic, toxic or infectious disorder or drug abuse.
6.Status epilepticus within 2 years prior to screening.
7.Seizures only occurring in a cluster pattern.
8.Subjects taking 2 of the following sodium channel blocking AEDs: phenytoin, carbamazepine, oxcarbazepine, or lamotrigine.
9.Subjects taking 2 AEDs with both being in the upper dose range.
10.Subjects taking more than 2 AEDs. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the present study is the proportion (%) of subjects meeting at least one of the five exit criteria (see Study Design) over a 16-week study period (from start of AED taper [Visit 4, Week 2 through end of double-blind monotherapy [Visit 9, Week 18]).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Seizure data will be collected for the subject during the baseline period and seizure rate will be calculated at each visit so that exit criteria can be assessed. |
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E.5.2 | Secondary end point(s) |
To evaluate the efficacy of eslicarbazepine acetate monotherapy at a dose of 1200 mg/day in subjects with partial epilepsy not well controlled by current AEDs.
To evaluate the safety of eslicarbazepine acetate monotherapy in subjects with partial epilepsy not well controlled by current AEDs.
To evaluate the population pharmacokinetics (PK) of eslicarbazepine acetate monotherapy subjects with partial epilepsy not well controlled by current AEDs. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Proportion (%) of subjects that are seizure-free during the 10-week (Weeks 9 through 18) double-blind monotherapy treatment. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
no comparator, randomization in two dose arms, historical control study design |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Bulgaria |
Canada |
Czech Republic |
Serbia |
Ukraine |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 30 |