Efficacy and Safety Study of Once-Daily Extended-Release Levetiracetam in Drug-resistant Focal Onset Seizures

Prior treatment

• History of status epilepticus in the past 3 months prior to screening.
• Diagnosis of active psychiatric disease, except depressed subjects on stable doses of selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors for at least 12 weeks prior to screening.
• History of prior suicide attempt or imminent risk of self-harm based on investigator’s judgment or with a “yes” answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSR-S).
• Participation in a study involving administration of an investigational product within one month prior to screening or within five half-lives of the previous study investigational compound, whichever is longer.

Other illness

• Presence of primary generalized epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
• Seizure clusters where individual seizures cannot be counted.
• History of non-epileptic seizures.
• Evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic or renal disease, neoplastic malignancies etc.) that in the opinion of the investigator could affect the subject's safety or trial conduct.
• Neurodegenerative and other progressive neurological disorders.
• History of drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-V) and/or positive drug screening other than prescribed drugs.
• Alcohol abuse as per Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-V) in the past year.
• Positive for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) or Human Immunodeficiency Virus (HIV) infection at screening, with active, clinically significant viral infections.
• Subjects presenting symptoms of coronavirus disease COVID-19.
• Known allergic reaction or intolerance to levetiracetam or other pyrrolidone derivatives or to any of the excipients.

Lab values

• Laboratory values at screening: • Platelets < 100,000/mm3 • Absolute neutrophil count < 1500/mm3 • Haemoglobin < 10.0g/dL • Aspartate aminotransferase or alanine aminotransferase > 3x upper limit of normal • Estimated Glomerular Filtration Rate < 80
• Subjects with a diagnosis of Congenital Short QT Syndrome (SQTS). Subjects with a family history of Congenital Short QT Syndrome (SQTS) or family history of sudden death of unknown cause.
• The corrected QT interval by Fredericia (QTcF) ≥ 450 msec in male and 470 msec in female subjects.

Other

• Body weight < 50kg.
• Current use of levetiracetam.
• Women who are currently pregnant, who intend to become pregnant during the study, or who are breastfeeding.

• Male and female, between 12 and 80 years of age, both inclusive for Spain, Poland and Bulgaria while the other countries will include only adult subjects.
• Willingness and capability to provide informed consent form (ICF), be compliant with study procedures such as eDiary completion, be compliant with background anti-seizure medication (ASM) and Investigational Medicinal Product (IMP) intake.
• Diagnosis of epilepsy with Focal-onset seizures (FOS) with or without secondary generalization according to the International League Against Epilepsy Classification of epileptic seizures.
• On stable doses of ASM for at least 4 weeks prior to screening. List of allowed ASM medications are provided in Appendix 18.2.
• Confirmed drug-resistant FOS despite 1-3 stable ASM with at least 6 seizures during the 8 week observational period
• Patients who have Vagal Nerve Stimulator (VNS) must have stable settings > 3 months prior to screening and expected to remain unchanged during the duration of the study
• Females of childbearing potential, if not abstinent, should use a highly effective contraception, started 60 days prior to study entry and 30 days after end of study drug administration: Combined (Estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: -Oral -Intravaginal -Transdermal; Progesterone-only hormonal contraception associated with inhibition of ovulation -Oral -Injectable -Implantable; Intrauterine device; Intrauterine hormone-releasing system; Bilateral tubal occlusion; Vasectomized partner; Sexual abstinence. See Appendix 18.1 for additional details.
• Females of non-childbearing potential: either surgically sterilized (e.g. bilateral tubal ligation), had undergone hysterectomy or is at least 1 year postmenopausal (amenorrhea duration of at least 12 months)
• Sexually active males with partner of childbearing potential commit to use an acceptable method of birth control consistently and correctly (oral, transdermal, systemic or implant contraception birth control, intrauterine devices) for 90 days after the last study drug administration.