A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy
Condition: Drug-Resistant Epilepsy; Focal-Onset Seizures
MeSH terms: Epilepsy; Seizures; Drug Resistant Epilepsy
Intervention: Padsevonil; Placebo
Intervention description: Padsevonil in different dosages.; Placebo will be provided matching padsevonil.
Intervention MeSH terms: Padsevonil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 232.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Epilepsy; Padsevonil

Summary:

      The purpose of the study is to evaluate the efficacy, safety and tolerability of the 3
      selected dose regimens of padsevonil (PSL) administered concomitantly with up to 3
      anti-epileptic drugs (AEDs) compared with placebo for treatment of observable focal-onset
      seizures in subjects with drug-resistant epilepsy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE)
             criteria at least 3 years before study entry

          -  Subject has failed to achieve seizure control with >=4 tolerated and appropriately
             chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that
             were individually optimized for adequate dose and duration. Prior discontinued AED
             treatment would need to be assessed by the Investigator considering the patient
             medical records and patient and/or caregiver interview. 'Prior AED' is defined as all
             past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)

          -  Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal
             aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic))
             per month

          -  Current treatment with an individually optimized and stable dose of at least 1 and up
             to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional
             Vagus Nerve Stimulation (VNS) or other neurostimulation treatments

        Exclusion Criteria:

          -  Subject has a history of or signs of generalized or combined generalized and focal
             epilepsy

          -  Cluster seizures which are uncountable in the previous 8 weeks before study entry and
             during 4 weeks prospective baseline

          -  Current treatment with carbamazepine, phenytoin, primidone, phenobarbital

          -  Current treatment/ use of (non-AED) prescription, nonprescription, dietary (eg,
             grapefruit or passion fruit), or herbal products that are potent inducers or
             inhibitors of the CYP3A4 or 2C19 pathway for 2 weeks (or 5 half-lives, whichever is
             longer) prior to the Baseline Visit

          -  Subjects taking sensitive substrates of CYP2C19 for 2 weeks (or 5 half-lives,
             whichever is longer) prior to the Baseline Visit

          -  Subject has been taking vigabatrin less than 2 years at study entry

          -  Subject has been taking felbamate for less than 12 months

          -  Subject taking retigabine for less than 4 years

          -  Current treatment with benzodiazepines (i.e. GABA-A-ergic drugs like zolpidem,
             zaleplon, or zopiclone, excluding GABA-A-ergic AEDs) <3 times per week for emergencies

          -  Subject has a current medical condition that occurred within the last 12 months which,
             in the opinion of the investigator, could compromise his/her safety or ability to
             participate in this study