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

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

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.

Study Overview

• Status: Terminated
• Conditions: Drug-Resistant Epilepsy; Focal-Onset Seizures
• Intervention / Treatment: Drug: Padsevonil

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia
    • Ep0093 855
  • Clayton, Australia
    • Ep0093 857
  • Fitzroy, Australia
    • Ep0093 850
  • Heidelberg, Australia
    • Ep0093 853
  • Herston, Australia
    • Ep0093 859
  • Melbourne, Australia
    • Ep0093 852
  • Randwick, Australia
    • Ep0093 856
  • Westmead, Australia
    • Ep0093 854
• Belgium
  • Brugge, Belgium
    • Ep0093 102
  • Brussels, Belgium
    • Ep0093 101
  • Gent, Belgium
    • Ep0093 105
  • Leuven, Belgium
    • Ep0093 100
  • Ottignies, Belgium
    • Ep0093 107
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina
    • Ep0093 075
  • Tuzla, Bosnia and Herzegovina
    • Ep0093 082
• Bulgaria
  • Blagoevgrad, Bulgaria
    • Ep0093 150
  • Pleven, Bulgaria
    • Ep0093 151
  • Pleven, Bulgaria
    • Ep0093 153
  • Pleven, Bulgaria
    • Ep0093 156
  • Sofia, Bulgaria
    • Ep0093 152
  • Sofia, Bulgaria
    • Ep0093 154
  • Sofia, Bulgaria
    • Ep0093 155
• Canada
  • Greenfield Park, Canada
    • Ep0093 200
  • London, Canada
    • Ep0093 205
  • Montréal, Canada
    • Ep0093 201
• Croatia
  • Zagreb, Croatia
    • Ep0093 125
• Czechia
  • Brno, Czechia
    • Ep0093 254
  • Ostrava, Czechia
    • Ep0093 255
  • Praha, Czechia
    • Ep0093 250
  • Praha, Czechia
    • Ep0093 253
  • Praha 6, Czechia
    • Ep0093 251
• Denmark
  • Aarhus, Denmark
    • Ep0093 016
  • Odense, Denmark
    • Ep0093 015
• Estonia
  • Tallin, Estonia
    • Ep0093 276
  • Tallinn, Estonia
    • Ep0093 277
  • Tartu, Estonia
    • Ep0093 275
• Finland
  • Tampere, Finland
    • Ep0093 027
• France
  • Clermont-Ferrand, France
    • Ep0093 307
  • Dijon, France
    • Ep0093 309
  • Lille, France
    • Ep0093 300
  • Montpellier, France
    • Ep0093 302
  • Rennes, France
    • Ep0093 303
  • Strasbourg, France
    • Ep0093 301
• Germany
  • Berlin, Germany
    • Ep0093 365
  • Bernau, Germany
    • Ep0093 362
  • Bielefeld, Germany
    • Ep0093 363
  • Bonn, Germany
    • Ep0093 358
  • Frankfurt, Germany
    • Ep0093 350
  • Freiburg, Germany
    • Ep0093 360
  • Jena, Germany
    • Ep0093 368
  • Kehl, Germany
    • Ep0093 366
  • Leipzig, Germany
    • Ep0093 357
  • Marburg, Germany
    • Ep0093 353
  • München, Germany
    • Ep0093 354
  • Münster, Germany
    • Ep0093 351
  • Osnabrück, Germany
    • Ep0093 356
  • Tübingen, Germany
    • Ep0093 352
• Greece
  • Thessaloníki, Greece
    • Ep0093 426
  • Thessaloníki, Greece
    • Ep0093 427
• Hungary
  • Budapest, Hungary
    • Ep0093 400
  • Budapest, Hungary
    • Ep0093 403
  • Debrecen, Hungary
    • Ep0093 402
• Ireland
  • Cork, Ireland
    • Ep0093 035
• Italy
  • Bologna, Italy
    • Ep0093 462
  • Cagliari, Italy
    • Ep0093 450
  • Foggia, Italy
    • Ep0093 451
  • Foggia, Italy
    • Ep0093 461
  • Milano, Italy
    • Ep0093 452
  • Pavia, Italy
    • Ep0093 459
  • Pozzilli, Italy
    • Ep0093 458
  • Roma, Italy
    • Ep0093 455
  • Roma, Italy
    • Ep0093 457
  • Roma, Italy
    • Ep0093 460
• Japan
  • Asahikawa, Japan
    • Ep0093 526
  • Asaka, Japan
    • Ep0093 501
  • Bunkyō-Ku, Japan
    • Ep0093 521
  • Fukuoka, Japan
    • Ep0093 511
  • Hamamatsu, Japan
    • Ep0093 504
  • Hiroshima, Japan
    • Ep0093 505
  • Hōfu, Japan
    • Ep0093 513
  • Itami, Japan
    • Ep0093 507
  • Kyoto, Japan
    • Ep0093 514
  • Nagakute, Japan
    • Ep0093 512
  • Niigata, Japan
    • Ep0093 510
  • Saitama, Japan
    • Ep0093 515
  • Shizuoka, Japan
    • Ep0093 509
  • Yonago, Japan
    • Ep0093 529
• Lithuania
  • Kaunas, Lithuania
    • Ep0093 703
  • Vilnius, Lithuania
    • Ep0093 702
• Mexico
  • Culiacán, Mexico
    • Ep0093 553
  • Mexico, Mexico
    • Ep0093 552
• Poland
  • Gdańsk, Poland
    • Ep0093 601
  • Grodzisk Mazowiecki, Poland
    • Ep0093 607
  • Katowice, Poland
    • Ep0093 605
  • Katowice, Poland
    • Ep0093 616
  • Kraków, Poland
    • Ep0093 603
  • Kraków, Poland
    • Ep0093 614
  • Lublin, Poland
    • Ep0093 604
  • Lublin, Poland
    • Ep0093 610
  • Nowa Sól, Poland
    • Ep0093 606
  • Poznań, Poland
    • Ep0093 600
  • Poznań, Poland
    • Ep0093 609
  • Świdnik, Poland
    • Ep0093 602
• Romania
  • Bucuresti, Romania
    • Ep0093 926
• Serbia
  • Belgrade, Serbia
    • Ep0093 327
• Slovakia
  • Bardejov, Slovakia
    • Ep0093 004
• Spain
  • Alicante, Spain
    • Ep0093 662
  • Barakaldo, Spain
    • Ep0093 668
  • Barcelona, Spain
    • Ep0093 651
  • Barcelona, Spain
    • Ep0093 652
  • Barcelona, Spain
    • Ep0093 664
  • Córdoba, Spain
    • Ep0093 666
  • Hospitalet de Llobregat, Spain
    • Ep0093 658
  • Madrid, Spain
    • Ep0093 656
  • Madrid, Spain
    • Ep0093 660
  • Madrid, Spain
    • Ep0093 667
  • Madrid, Spain
    • Ep0093 674
  • Málaga, Spain
    • Ep0093 659
  • Terrassa, Spain
    • Ep0093 665
  • Valencia, Spain
    • Ep0093 657
  • Valladolid, Spain
    • Ep0093 653
• Turkey
  • Istanbul, Turkey
    • Ep0093 900
  • Istanbul, Turkey
    • Ep0093 901
  • Istanbul, Turkey
    • Ep0093 904
  • Istanbul, Turkey
    • Ep0093 906
  • Istanbul, Turkey
    • Ep0093 909
• United Kingdom
  • Birmingham, United Kingdom
    • Ep0093 752
  • Brighton, United Kingdom
    • Ep0093 766
  • Swansea, United Kingdom
    • Ep0093 751
  • Swansea, United Kingdom
    • Ep0093 753
  • Swansea, United Kingdom
    • Ep0093 764
• United States
  • Arizona
    • Chandler, Arizona, United States, 85226
      • Ep0093 839
  • California
    • La Jolla, California, United States, 92037
      • Ep0093 815
    • San Francisco, California, United States, 94115
      • Ep0093 801
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Ep0093 803
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Ep0093 638
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Ep0093 707
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Ep0093 822
    • Bethesda, Maryland, United States, 20817
      • Ep0093 818
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Ep0093 889
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Ep0093 645
    • Saint Paul, Minnesota, United States, 55102
      • Ep0093 817
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Ep0093 806
  • New York
    • Bronx, New York, United States, 10467-24 01
      • Ep0093 895
    • Syracuse, New York, United States, 13210
      • Ep0093 893
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Ep0093 890
    • Charlotte, North Carolina, United States, 28204
      • Ep0093 884
  • Ohio
    • Columbia, Ohio, United States, 43210
      • Ep0093 642
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Ep0093 802
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Ep0093 838
    • Nashville, Tennessee, United States, 37232
      • Ep0093 835
  • Texas
    • Austin, Texas, United States, 78701
      • Ep0093 805
    • Austin, Texas, United States, 78758
      • Ep0093 844
    • Round Rock, Texas, United States, 78681
      • Ep0093 824
    • San Antonio, Texas, United States, 78229
      • Ep0093 870
  • Washington
    • Renton, Washington, United States, 98055
      • Ep0093 639

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Padsevonil; 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; Pharmaceutical Form: film-coated tablet; Route of Administration: Oral use

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2018
• Primary Completion (Actual): December 11, 2020
• Study Completion (Actual): December 11, 2020

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: November 30, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Padsevonil; Drug-Resistant Epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Drug Resistant Epilepsy
• Other Study ID Numbers: EP0093; 2017-003241-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No