E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epilepsy - Refractory Partial Onset Seizures |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061334 |
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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 and safety of levetiracetam (LEV) used as adjunctive treatment in pediatric subjects age 1 month to less than 4 years with refractory partial onset seizures. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Before any study procedures are initiated for any subject in this study, an IRB/IEC approved written informed consent form will be properly executed and documented. To be eligible to participate in the study, a subject must meet each of the following criteria. • The subject’s parent(s) or legally authorized representative(s) must give consent and sign and date the IRB/IEC approved written informed consent form. • Subject must have a diagnosis of epilepsy with refractory partial onset seizures (i.e., seizures of focal onset), whether or not secondarily generalized. • Subject must be male or female from 1 month to less than 4 years of age. • Must be a subject for whom the Investigator believes that past or current anti-epileptic drug (AED) treatment is unsatisfactory in terms of efficacy and/or safety. • Must be a subject for whom alternative treatment with levetiracetam may be of benefit. • Subject must be on a stable regimen of one or a maximum of two other AEDs for the Selection and Evaluation periods of the study. • Minor adjustments to the dose of current AEDs are allowed only prior to Day -8. • Subject has no additions of new AEDs or deletions of current AEDs that have been observed for at least 2 weeks prior to Day -8. • Subject may have Vagus Nerve Stimulation (VNS) which has been implanted for at least 6 months prior to Day -8; the settings must be stable for at least 2 months prior to Day -8. Activated VNS must be counted as one of the two AEDs. • Subject must have experienced at least two partial onset seizures (i.e., seizures of focal onset), with or without secondary generalization during each 7-day period during the 2 weeks prior to Day -8. • Subjects 1 month to less than 6 months of age must experience at least two, partial onset seizures (i.e., seizures of focal onset), whether or not secondarily generalized during the 48-hour video-EEG performed prior to randomization on Day 1. These seizures do not need to be accompanied by a corresponding clinical event. • Subjects 6 months to less than 1 year of age, subjects 1 year to less than 2 years of age and subjects 2 years to less than 4 years of age must experience at least two partial onset seizures (i.e., seizures of focal onset), whether or not secondarily generalized, during the 48-hour video-EEG performed prior to randomization on Day 1. These seizures must be accompanied by a corresponding clinical event as noted on either video or as reported by a qualified observer, such as a medical doctor or a nurse with significant neurology training and experience. • If epilepsy surgery has been performed prior to study entry, then the subjects must have a documented failed epilepsy surgery outcome at least 4 weeks prior to Day -8. • The use of intermittent benzodiazepines is allowed as long as the frequency is not greater than one single administration per week for at least 2 weeks prior to Day -8 and throughout study participation. • If benzodiazepines are used more than once a week, they must be considered as one of the AEDs. |
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E.4 | Principal exclusion criteria |
Subjects must be excluded if they meet any of the following criteria: • Subject is taking any medication (other than their concomitant AED(s)) that influences the central nervous system (CNS) for which they have not been on a stable regimen for at least 1 month prior to Day -8. • Subject is taking any medication that may interfere with the absorption, distribution, metabolism, or excretion of the concomitant AEDs or levetiracetam during the course of the study. • Subject has received any investigational medication or device within thirty (30) days prior to Day -8. • Subject has taken levetiracetam prior to the study. • Subjects using felbamate who have presented with clinically significant abnormalities with WBC’s, RBC’s, platelets, and/or hepatic function during felbamate treatment, and subjects who are taking felbamate less than one year from the date of Day -8. • Subject has a treatable seizure etiology, (i.e., febrile seizures). • Subject has a history of status epilepticus requiring hospitalization during the 1 month prior to Day -8, except for status epilepticus occurring during the first 10 days of life. • Subject has a current diagnosis of Lennox-Gastaut syndrome. • Subject is on a ketogenic diet (currently or within 30 days prior to Day -8). • Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen and Landau-Kleffner diseases. • Subject has clinically significant deviations from reference range values for renal function or any of the other laboratory parameters required for this study, as determined by the Investigator. • Subject has any clinically significant acute or chronic illness (as determined during the physical examination or from other information available to the Investigator). • Subject has an allergy to pyrrolidine derivatives or a history of multiple drug allergies. • Subject is known to have a terminal illness. • Subject has a disorder or condition that may interfere with the absorption, distribution, metabolism, or excretion of medications. • Subject has a history of or presence of pseudoseizures. • Subject has any medical condition that might interfere with the subject’s study participation (i.e., serious infection, scheduled elective surgery, severe scalp eczema, etc). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analyses will be based on mITT and PP populations. The primary efficacy variable, Responder Rate, for total partial onset seizures for subjects in all age groups is defined as the number of subjects with a ≥ 50% reduction in their average daily frequency (ADF) of partial onset seizures recorded on the 48-hour Evaluation video-EEG compared to the 48-hour Selection video-EEG.
Safety parameters will be: physical and neurological examinations, adverse events, vital signs, and laboratory tests, including blood chemistry, levetiracetam (LEV) levels, and hematology.
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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 | Information not present in EudraCT |
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 | 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.8.5 | 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 |
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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
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The end of the trial is defined as the date of Database Lock as, at that time, interactions between the Sponsor and the Investigator with possible impact on subjects data have ended.
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |