Refractory epilepsy suffering from partial onset seizures MedDRA version: 8.1 Level: LLT Classification code 10061334 Term: Partial seizures
Conditions
Interventions
Product Name: Levetiracetam
Product Code: L059
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Levetiracetam
CAS Number: 102767-28-2
Current Sponsor code: ucb L059
Other descriptive
Sponsors
UCB S.A.
UCB Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed and dated written informed consent. Signed and dated written assent if applicable. • Subjects suffering from partial onset seizures according to the ILAE classification of epileptic seizures, whether or not secondarily generalized. • Subjects with diagnosed epilepsy for a minimum of 6 months prior to the Selection Visit. • An EEG must be present in the hospital file but it may be normal if taken interictaly. • Presence of the following during the eight weeks of the Baseline Period: at least eight partial seizures (type IA, IB, or IC) with or without secondary generalization and at least two partial seizures in each 4-week interval of the Baseline Period. • Subjects are reliable and mentally capable of adhering to the protocol, according to Investigator judgment. • Male/female subjects, 12 to 70 years of age inclusive, weighing at least 50 kg at Visit 1. • Female subjects without childbearing potential are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method. The subjects must understand the consequences and potential risks of inadequately protected sexual activity, be educated about and understand the proper use of the contraceptive method, and undertake to inform the Investigator of any potential change in status. • Subjects on a stable dose for at least four weeks before the Selection Visit (Visit 1) of at least one and no more than three other concomitant antiepileptic drugs (AEDs). Benzodiazepines will be considered as an AED if taken at a frequency greater than an average of once a week; whatever the indication. • If on Vagal Nerve Stimulator (VNS) as long as the setting is stable for at least 3 months prior to Visit 1. The VNS will be counted as one AED. • If past epilepsy surgery, documentation of failure of surgery outcome. • Previous CT scan or MRI to confirm the subjects are free of neoplasia, progressive cerebral disease or any other progressively neurodegenerative disease. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Females who are lactating or pregnant. • Known alcohol or drug addiction or abuse. • Known allergic reaction or intolerance to pyrrolidine derivatives (such as piracetam, succinimide, proline and rolitetracycline) and/or excipients (not exclusively but principally to lactose, corn starch, cellulose). • History of status epilepticus within three months prior to the Selection Visit. • History or current neoplasia, progressive cerebral disease or any other progressive neurodegenerative disease. • Subjects whose seizures cannot reliably be counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries). • Use of any medication (other than the concomitant AED) that influences the central nervous system (CNS) unless on a stable regimen for at least 4 weeks prior to the Selection Visit. Antidepressants (except amitriptyline, mianserin and fluoxetine), anxiolytics and hypnotics are allowed. • Neuroleptics and traditional herb AEDs are not allowed. • Subjects on felbamate. • Subjects on ketogenic diet. • Presence of another clinical disease (cardiovascular, hepatic, renal, auto-immune or associated with hematology, neurology or psychiatry) or any other disease that would interfere with the absorption, distribution, metabolism or excretion of the investigational product or with the subjects’ ability to reliably complete the daily record card. • History of recurrent psychotic or major affective disorder or suicide attempts. • History or presence of pseudoseizures. • Clinically significant abnormal laboratory values as assessed by the Investigator. • History of poor compliance with visit schedule or medication intake. • Subjects taking part in another clinical/pharmacological study in the 30 days prior to Visit 1. • Subjects having already been treated with an adequate dose of LEV (at least 1000 mg/day) for more than 4 weeks and discontinued due to reasons related to lack of efficacy or due to tolerability problems. • Subjects with any medical or surgical condition that might interfere with the subject’s study participation, i.e. scheduled elective surgery, etc.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of LEV XR 2 x 500 mg/day, once daily as adjunctive therapy in the treatment of refractory epilepsy subjects 12 to 70 years with partial onset seizures in comparison with placebo.;Secondary Objective: To evaluate the safety and tolerability of LEV XR 2 x 500 mg/day, once daily as adjunctive therapy in the treatment of refractory epilepsy subjects 12 to 70 years with partial onset seizures.;Primary end point(s): Two analysis populations will be defined as intention-to-treat (ITT) and per-protocol (PP): • ITT will be defined as randomized subjects who received at least one dose of study medication. • PP will be ITT subjects excluding those with major protocol violations affecting the primary efficacy variable, to be determined during the pre-analysis meeting. The primary efficacy analysis, all secondary efficacy analyses, the exploratory efficacy analysis and all safety analyses will be performed on the ITT population. The primary efficacy variable analysis will also be analyzed on the PP population if more than 10% of the ITT population is excluded from the PP population. Efficacy Variables: The primary efficacy variable will be the partial onset (type I) seizure frequency per week over the treatment period. Safety Variables: Laboratory tests (blood), Adverse events (AEs), Physical and neurological examinations, Vital signs, Electrocardiogram, Body weight. Pharmacokinetics and Pharmacodynamics Variables: The plasma concentrations will be used in a population pharmacokinetic analysis aimed at comparing levetiracetam exposure between the two formulations. The population pharmacokinetic modeling methods will be described in a specific data analysis plan, and the results of the analysis will be reported separately. Plasma Concentration: At Visits 5, 6, 7, and Early Discontinuation Visit, a plasma sample will be drawn to measure the levetiracetam plasma concentrations. Ideally, the samples for the three different visits sh | — |
Countries
Finland
Outcome results
None listed