MedPath

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

Phase 3
Terminated
Conditions
Drug-Resistant Epilepsy
Focal-Onset Seizures
Interventions
Drug: Padsevonil
Drug: Placebo
Registration Number
NCT03739840
Lead Sponsor
UCB Biopharma SRL
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
232
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
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Padsevonil dosing regimen 1PlaceboSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Padsevonil dosing regimen 2PlaceboSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
PlaceboPlaceboSubjects randomized to the placebo group will receive a combination of several placebo tablets to maintain the blinding.
Padsevonil dosing regimen 3PlaceboSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Padsevonil dosing regimen 2PadsevonilSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Padsevonil dosing regimen 3PadsevonilSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Padsevonil dosing regimen 1PadsevonilSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)From Baseline until Safety Follow-Up (up to Week 23)

An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)From Baseline until Safety Follow-Up (up to Week 23)

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is as infection that requires treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

Change in Log-transformed Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance PeriodFrom Baseline over the 12 Week Maintenance Period (up to Week 16)

During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed seizure frequency from Baseline, with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (Yes or No) and Region (Europe, non-Europe) as categorical factors.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study WithdrawalFrom Baseline until Safety Follow-Up (up to Week 23)

An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was defined as any event not present before the initiation of the first dose of study treatment or any unresolved event already present before initiation of the first dose that worsened in intensity following exposure to the treatment.

Secondary Outcome Measures
NameTimeMethod
75% Responder Rate From Baseline Over the 12-week Maintenance PeriodFrom Baseline over the 12 Week Maintenance Period (up to Week 16)

The 75 % responder rate, where a responder was a participant experiencing a ≥75 % reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.

50% Responder Rate From Baseline Over the 12-week Maintenance PeriodFrom Baseline over the 12 Week Maintenance Period (up to Week 16)

The 50% responder rate, where a responder was a participant experiencing a ≥50% reduction in observable focal-onset seizure frequency from Baseline, over the 12-week Maintenance Period.

Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance PeriodFrom Baseline over the 12 Week Maintenance Period (up to Week 16)

During the study, participants kept diaries to record daily seizure activity. The percentage of participants who experienced a 50 % or greater reduction in seizure frequency per 28 days relative to Baseline (responders) were assessed.

Trial Locations

Locations (141)

Ep0092 150

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Blagoevgrad, Bulgaria

Ep0092 128

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Zagreb, Croatia

Ep0092 276

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Tallinn, Estonia

Ep0092 277

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Tallinn, Estonia

Ep0092 053

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Zürich, Switzerland

Ep0092 275

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Tartu, Estonia

Ep0092 427

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Thessaloníki, Greece

Ep0092 404

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Pécs, Hungary

Ep0092 508

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Sapporo, Japan

Ep0092 610

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Lublin, Poland

Ep0092 504

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Hamamatsu, Japan

Ep0092 505

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Hiroshima, Japan

Ep0092 539

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Kumamoto, Japan

Ep0092 512

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Nagakute, Japan

Ep0092 522

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Ōmura, Japan

Ep0092 530

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Ōsaka-sayama, Japan

Ep0092 926

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Bucuresti, Romania

Ep0092 845

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Washington, District of Columbia, United States

Ep0092 637

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Urbana, Illinois, United States

Ep0092 645

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Golden Valley, Minnesota, United States

Ep0092 878

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Brooklyn, New York, United States

Ep0092 080

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Bihać, Bosnia and Herzegovina

Ep0092 077

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Mostar, Bosnia and Herzegovina

Ep0092 154

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Sofia, Bulgaria

Ep0092 127

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Zagreb, Croatia

Ep0092 016

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Aarhus, Denmark

Ep0092 312

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Lyon, France

Ep0092 151

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Pleven, Bulgaria

Ep0092 125

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Zagreb, Croatia

Ep0092 015

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Odense, Denmark

Ep0092 350

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Frankfurt, Germany

Ep0092 363

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Bielefeld, Germany

Ep0092 254

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Brno, Czechia

Ep0092 376

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Regensburg, Germany

Ep0092 853

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Heidelberg, Australia

Ep0092 893

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Syracuse, New York, United States

Ep0092 861

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Camperdown, Australia

Ep0092 075

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Sarajevo, Bosnia and Herzegovina

Ep0092 082

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Tuzla, Bosnia and Herzegovina

Ep0092 126

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Zagreb, Croatia

Ep0092 852

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Melbourne, Australia

Ep0092 251

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Praha 6, Czechia

Ep0092 876

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New York, New York, United States

Ep0092 156

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Pleven, Bulgaria

Ep0092 426

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Thessaloníki, Greece

Ep0092 405

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Debrecen, Hungary

Ep0092 501

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Asaka, Japan

Ep0092 521

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Bunkyō-Ku, Japan

Ep0092 884

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Charlotte, North Carolina, United States

Ep0092 829

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Charlottesville, Virginia, United States

Ep0092 639

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Renton, Washington, United States

Ep0092 310

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Paris, France

Ep0092 403

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Budapest, Hungary

Ep0092 850

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Fitzroy, Australia

Ep0092 365

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Berlin, Germany

Ep0092 109

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Brussels, Belgium

Ep0092 107

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Ottignies, Belgium

Ep0092 362

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Bernau, Germany

Ep0092 357

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Leipzig, Germany

Ep0092 250

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Praha 5, Czechia

Ep0092 855

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Box Hill, Australia

Ep0092 258

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Ostrava, Czechia

Ep0092 892

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Bradenton, Florida, United States

Ep0092 642

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Columbus, Ohio, United States

Ep0092 802

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Philadelphia, Pennsylvania, United States

Ep0092 531

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Izumi, Japan

Ep0092 881

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Tucson, Arizona, United States

Ep0092 839

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Chandler, Arizona, United States

Ep0092 633

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Carlsbad, California, United States

Ep0092 629

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Orange, California, United States

Ep0092 641

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Jacksonville, Florida, United States

Ep0092 640

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Hialeah, Florida, United States

Ep0092 880

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Anderson, Indiana, United States

Ep0092 822

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Baltimore, Maryland, United States

Ep0092 638

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Fort Wayne, Indiana, United States

Ep0092 630

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Ames, Iowa, United States

Ep0092 889

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Boston, Massachusetts, United States

Ep0092 027

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Tampere, Finland

Ep0092 301

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Strasbourg, France

Ep0092 368

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Jena, Germany

Ep0092 425

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Ioánnina, Greece

Ep0092 428

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Thessaloníki, Greece

Ep0092 035

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Cork, Ireland

Ep0092 036

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Dublin, Ireland

Ep0092 452

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Milano, Italy

Ep0092 526

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Asahikawa, Japan

Ep0092 525

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Bunkyō-Ku, Japan

Ep0092 513

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Hōfu, Japan

Ep0092 507

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Itami, Japan

Ep0092 533

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Kure, Japan

Ep0092 514

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Kyoto, Japan

Ep0092 515

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Saitama, Japan

Ep0092 527

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Shinagawa-Ku, Japan

Ep0092 509

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Shizuoka, Japan

Ep0092 529

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Yonago, Japan

Ep0092 775

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Sandvika, Norway

Ep0092 605

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Katowice, Poland

Ep0092 616

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Katowice, Poland

Ep0092 603

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Kraków, Poland

Ep0092 614

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Kraków, Poland

Ep0092 620

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Lublin, Poland

Ep0092 606

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Nowa Sól, Poland

Ep0092 611

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Warszawa, Poland

Ep0092 615

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Wrocław, Poland

Ep0092 619

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Zamość, Poland

Ep0092 618

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Zgierz, Poland

Ep0092 612

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Łódź, Poland

Ep0092 952

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Aveiro, Portugal

Ep0092 950

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Matosinhos, Portugal

Ep0092 925

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Bucuresti, Romania

Ep0092 927

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Târgu-Mureş, Romania

Ep0092 325

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Novi Sad, Serbia

Ep0092 004

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Bardejov, Slovakia

Ep0092 327

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Belgrade, Serbia

Ep0092 662

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Alicante, Spain

Ep0092 651

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Barcelona, Spain

Ep0092 652

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Barcelona, Spain

Ep0092 658

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Barcelona, Spain

Ep0092 674

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Madrid, Spain

Ep0092 657

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Valencia, Spain

Ep0092 576

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Göteborg, Sweden

Ep0092 915

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Antalya, Turkey

Ep0092 913

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Ankara, Turkey

Ep0092 906

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Istanbul, Turkey

Ep0092 900

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Istanbul, Turkey

Ep0092 909

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Istanbul, Turkey

Ep0092 750

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Manchester, United Kingdom

Ep0092 908

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Trabzon, Turkey

Ep0092 766

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Brighton, United Kingdom

Ep0092 764

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Swansea, United Kingdom

Ep0092 575

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Linköping, Sweden

Ep0092 676

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Zaragoza, Spain

Ep0092 818

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Bethesda, Maryland, United States

Ep0092 882

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Portland, Oregon, United States

Ep0092 647

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Oklahoma City, Oklahoma, United States

Ep0092 644

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Minneapolis, Minnesota, United States

Ep0092 823

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Orlando, Florida, United States

Ep0092 803

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Honolulu, Hawaii, United States

Ep0092 707

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Lexington, Kentucky, United States

Ep0092 895

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Bronx, New York, United States

Ep0092 890

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Chapel Hill, North Carolina, United States

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