Study to Test the Safety and Efficacy of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the long-term safety and tolerability of Padsevonil administered at individualized doses as adjunctive treatment for subjects with drug-resistant epilepsy.

Official Title
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An Open-Label, Multicenter, Extension Study to Evaluate the Safety and Efficacy of Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult Subjects With Drug-Resistant Epilepsy

Conditions
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Drug-Resistant Epilepsy, Focal-Onset Seizures

Intervention / Treatment
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* Drug: Padsevonil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is an adult (18 years of age or more ) Subject with epilepsy who has completed 1 of the previous Padsevonil (PSL) studies which allow access to the present study Female subjects of child bearing potential must have a serum negative pregnancy test at the Entry Visit, which is confirmed to be negative by urine testing prior to further dispensing at each study visit thereafter. Subjects will be withdrawn from the study as soon as pregnancy is known. Female subjects will use an efficient form of contraception for the duration of the study and for a period of 3 months after their final dose of PSL. Exclusion Criteria: Subject has any severe medical, neurological, or psychiatric condition, or laboratory value which may have an impact on the safety of the subject Subject has active suicidal ideation as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the 'Since Last Visit' version of the Columbia-Suicide Severity Rating Scale (C-SSRS) Subject has >2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (>= l.5x ULN total bilirubin if known Gilbert's syndrome) at the Entry Visit Subject has a clinically-significant abnormality on electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study Subject has an abnormality on echocardiogram at last echocardiogram assessment, or foreseen in parent study as assessed by central reader that is accompanied by clinical symptoms or a Grade 2* (or higher)/moderate severity abnormality, or a history of rheumatic heart disease, or other known valvular abnormalities (*according to the ASE Guidelines, 2017; Zoghbi et al 2017) Female subject who plans to be pregnant or is breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Padsevonil<br>Padsevonil will be administered in an open-label manner. The individual starting dose of each subject will be the one at the end of the parent study. Once subjects enter EP0093 further individual dose adjustments are allowed after 1 week to the extent possible with the combination of tablet strengths available. | Drug: Padsevonil<br>* Pharmaceutical Form: film-coated tablet Route of Administration: Oral use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Participant and/or Caregiver or Observed by the Investigator During the Entire Study | An Adverse Event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event that was not present prior to the initiation of the first dose of study treatment in this study or any unresolved event already present before initiation of the first dose that worsens in intensity following exposure to the treatment. | From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years) | 
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal | An Adverse Event is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event that was not present prior to the initiation of the first dose of study treatment in this study or any unresolved event already present before initiation of the first dose that worsens in intensity following exposure to the treatment. | From Entry Visit (Week 0) until the Safety Follow-up Visit (up to approximately 2 years) | 
| Change From Baseline (From the Respective Parent Study [EP0091 or EP0092]) in Observable Focal-onset Seizure Frequency Over the Evaluation Period | Seizure frequency refers to 28-day adjusted frequency. Observable focal-onset seizures refer to Type IAl, IB, and IC (according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures, 1981). Focal-onset seizures include all Type I seizures. | From Baseline in respective parent study over the Evaluation Period (up to approximately 2 years) in this study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-Resistant Epilepsy, Padsevonil