| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Epilepsy - Refractory Partial Onset Seizures |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061334 |
| E.1.2 | Term | Partial seizures |
|
| 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 |
| The primary objective of this study is to obtain long-term descriptive safety and efficacy data in pediatric epileptic patients with partial onset seizures receiving long-term treatment with levetiracetam at individualized doses. This study in conjunction with Study N157 (UCB’s other long-term, follow-up pediatric study) will be used to fulfill the requirement from the FDA written request “to determine the long-term safety of levetiracetam as adjunctive therapy in the treatment of partial onset seizures in pediatric patients”. |
|
| E.2.2 | Secondary objectives of the trial |
• To allow pediatric patients with partial onset seizures whose parent(s) or legally authorized representative(s) gave consent for them to participate in the previous levetiracetam pediatric exclusivity trial (N01009) and patients 4 to 16 years of age, inclusive, the opportunity to receive open-label levetiracetam treatment.
• To continue to study the potential cognitive and behavioral effects of levetiracetam in children.
• To ensure the safety of study participants by providing standardized follow-up. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Before any study procedures are initiated for any patient in this study, an IRB/IEC approved written informed consent form will be properly executed and documented. To be eligible to participate in this study, the following criteria must be met:
• Patient’s parent(s)/legally authorized representative(s) must have consented for the patient to participate in a previous levetiracetam pediatric trial (N01009). The last visit of the previous levetiracetam study should occur on the same day as the 1st visit of this study. Patients having been screened, but not eligible for study N01009, may be considered to enter this study. Visit 1 will occur on the same day as the screen failure.
• Patients not entering from study N01009 must be 4 to 16 years of age, inclusive.
• The patient’s parent(s)/legally authorized representative(s) must give consent and sign and date the IRB/IEC approved written informed consent form for N01148, if applicable, the patient will sign an assent.
• Patient enrolling directly into N01148 must have a confirmed diagnosis of epilepsy with partial onset seizures, whether or not secondarily generalized for a minimum of six months prior to the Screening Visit.
• Be a patient for whom the treatment of levetiracetam would be of potential benefit.
• Be a male, or a non-pregnant, non-nursing female. Females of childbearing potential must be using a medically acceptable method of contraception or must agree to abstain from sexual contact. Abstinence must be discussed with UCB or designee on a case by case basis. Females of childbearing potential will have pregnancy tests performed at each scheduled visit during the course of the study.
• Patient may have Vagus Nerve Stimulation (VNS), the settings should be stabilized for at least 2 months prior to Visit 1. Activated VNS must be counted as one of the two AEDs.
• Patient must be on a stable regimen of one or a maximum of two other AEDs. No additions of new AEDs or deletions of previous AEDs is allowed for at least two weeks prior to the Screening Visit for patients enrolling directly into N01148.
• Patient not entering from study N01009 must have had at least 1 partial onset seizures during the four weeks prior to the Screening Visit.
• Patient and/or their parent(s)/legally authorized representative(s) must be able to cooperate with the Investigator and study personnel involved in carrying out the study.
• Patients 4 to 16 years of age, inclusive directly enrolling must have an Intelligence Quotient (IQ) of at least 65 at the Screening Visit.
• The patient and patient's parent(s) or legally authorized representative(s) must be fluent in English.
• For patients enrolling directly into N01148 (4 to 16 years of age, inclusive), and if epilepsy surgery has been performed, then the patient should have a documented failed epilepsy surgery outcome of greater than 6 months prior to the Screening Visit.
• The patient’s epilepsies should be classifiable according to the “Proposal for Revised Classification of Epilepsies and Epileptic Syndromes” and his/her seizures should be classifiable according to the “Proposal for Revised Clinical and Electroencephalographic Classification of Epileptic Seizures”.
• If enrolling from N01009 and if epilepsy surgery has been performed, then the patient should have a documented failed epilepsy surgery outcome of at least 4 weeks prior to Visit 1. |
|
| E.4 | Principal exclusion criteria |
Patients must be excluded if they meet any of the following criteria:
• Participating in any other clinical trial of another investigational drug or device during this study.
• Patients enrolling directly into N01148 (4 to 16 years of age, inclusive), must not have had previous treatment with levetiracetam unless, in the opinion of the investigator, the patient’s previous treatment was inadequate in dose or duration to provide an accurate assessment of the therapy, or the effect of levetiracetam was confounded by concomitant medication.
• Are on a ketogenic diet (during the course of this study).
• Have seizures too close together to accurately count (i.e., the patient’s seizures must be countable).
• Have clinically significant deviations from reference range values for laboratory parameters as determined by the investigator on the blood sample of the last visit of the previous study or of the Screening Visit for patients 4 to 16 years of age, inclusive, enrolling directly into N01148.
• Have any clinically significant acute or chronic illness (as determined during the physical examination or from other information available to the investigator) such as, but not limited to: cardiac disease, liver disease, renal disease, or psychiatric illness.
• Patient has a treatable seizure etiology other than epilepsy (i.e., febrile seizures).
• Patient has a history of status epilepticus, which required hospitalization during one month prior to Visit 1, except for status epilepticus occurring during the first 10 days of life.
• Patient has a current diagnosis of Lennox-Gastaut Syndrome.
• Patient has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen and Landau-Kleffner diseases.
• Patient has a history of an allergy to pyrrolidine derivatives or a history of multiple drug allergies.
• Patient is known to have a terminal illness.
• Patient has any disorder or condition that may interfere with the absorption, distribution, metabolism, or excretion of medications.
• Patient has a history of or presence of pseudoseizures.
• Patient has any medical condition that might interfere with the subject’s study participation (i.e., serious infection, scheduled elective surgery, etc). • Patient has a current psychiatric diagnosis of severe Attention Deficit Hyperactivity Disorder (ADHD), severe behavior disorder or severe learning disorder.
• Patient is receiving phenobarbital or primidone on a routine or chronic basis. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
All patients who take at least one dose of levetiracetam (Intent to Treat) in this study may be included in the analysis of this study. Efficacy variables: The primary efficacy variable is the percentage change of partial (type I) seizure frequency per week over time from baseline during the treatment period. Secondary Efficacy Variables:
• Percentage change of total (types I, II, III) seizure frequency per week from baseline over time
• Total and partial seizure frequency per week over time
• Change from baseline of partial and total seizure frequency per week over time
• Responder rate
• Maximum seizure-free interval
• Continuously seizure-free during study
• Seizure types
• Global Evaluation Scale Safety variables:
• Laboratory Tests
• Adverse Events
• Electrocardiogram (ECG)
• Physical and Neurological Examinations
• Vital Signs
• Leiter International Performance Scale - Revised (Leiter-R)
• Achenbach Child Behavior Checklist (CBCL)
• Bayley Scales of Infant Development-II (BSID-II) |
|
| 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 | 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 | 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 | No |
| E.8.1.2 | Open | Yes |
| 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.8.4.1 | 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 | 50 |
| 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
| |
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 9 |
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