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

December 19, 2022 updated by: UCB Biopharma SRL

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety 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 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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

232

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Box Hill, Australia
        • Ep0092 855
      • Camperdown, Australia
        • Ep0092 861
      • Fitzroy, Australia
        • Ep0092 850
      • Heidelberg, Australia
        • Ep0092 853
      • Melbourne, Australia
        • Ep0092 852
  • Belgium
      • Brussels, Belgium
        • Ep0092 109
      • Ottignies, Belgium
        • Ep0092 107
  • Bosnia and Herzegovina
      • Bihać, Bosnia and Herzegovina
        • Ep0092 080
      • Mostar, Bosnia and Herzegovina
        • Ep0092 077
      • Sarajevo, Bosnia and Herzegovina
        • Ep0092 075
      • Tuzla, Bosnia and Herzegovina
        • Ep0092 082
  • Bulgaria
      • Blagoevgrad, Bulgaria
        • Ep0092 150
      • Pleven, Bulgaria
        • Ep0092 151
      • Pleven, Bulgaria
        • Ep0092 156
      • Sofia, Bulgaria
        • Ep0092 154
  • Croatia
      • Zagreb, Croatia
        • Ep0092 125
      • Zagreb, Croatia
        • Ep0092 126
      • Zagreb, Croatia
        • Ep0092 127
      • Zagreb, Croatia
        • Ep0092 128
  • Czechia
      • Brno, Czechia
        • Ep0092 254
      • Ostrava, Czechia
        • Ep0092 258
      • Praha 5, Czechia
        • Ep0092 250
      • Praha 6, Czechia
        • Ep0092 251
  • Denmark
      • Aarhus, Denmark
        • Ep0092 016
      • Odense, Denmark
        • Ep0092 015
  • Estonia
      • Tallinn, Estonia
        • Ep0092 276
      • Tallinn, Estonia
        • Ep0092 277
      • Tartu, Estonia
        • Ep0092 275
  • Finland
      • Tampere, Finland
        • Ep0092 027
  • France
      • Lyon, France
        • Ep0092 312
      • Paris, France
        • Ep0092 310
      • Strasbourg, France
        • Ep0092 301
  • Germany
      • Berlin, Germany
        • Ep0092 365
      • Bernau, Germany
        • Ep0092 362
      • Bielefeld, Germany
        • Ep0092 363
      • Frankfurt, Germany
        • Ep0092 350
      • Jena, Germany
        • Ep0092 368
      • Leipzig, Germany
        • Ep0092 357
      • Regensburg, Germany
        • Ep0092 376
  • Greece
      • Ioánnina, Greece
        • Ep0092 425
      • Thessaloníki, Greece
        • Ep0092 426
      • Thessaloníki, Greece
        • Ep0092 427
      • Thessaloníki, Greece
        • Ep0092 428
  • Hungary
      • Budapest, Hungary
        • Ep0092 403
      • Debrecen, Hungary
        • Ep0092 405
      • Pécs, Hungary
        • Ep0092 404
  • Ireland
      • Cork, Ireland
        • Ep0092 035
      • Dublin, Ireland
        • Ep0092 036
  • Italy
      • Milano, Italy
        • Ep0092 452
  • Japan
      • Asahikawa, Japan
        • Ep0092 526
      • Asaka, Japan
        • Ep0092 501
      • Bunkyō-Ku, Japan
        • Ep0092 521
      • Bunkyō-Ku, Japan
        • Ep0092 525
      • Hamamatsu, Japan
        • Ep0092 504
      • Hiroshima, Japan
        • Ep0092 505
      • Hōfu, Japan
        • Ep0092 513
      • Itami, Japan
        • Ep0092 507
      • Izumi, Japan
        • Ep0092 531
      • Kumamoto, Japan
        • Ep0092 539
      • Kure, Japan
        • Ep0092 533
      • Kyoto, Japan
        • Ep0092 514
      • Nagakute, Japan
        • Ep0092 512
      • Saitama, Japan
        • Ep0092 515
      • Sapporo, Japan
        • Ep0092 508
      • Shinagawa-Ku, Japan
        • Ep0092 527
      • Shizuoka, Japan
        • Ep0092 509
      • Yonago, Japan
        • Ep0092 529
      • Ōmura, Japan
        • Ep0092 522
      • Ōsaka-sayama, Japan
        • Ep0092 530
  • Norway
      • Sandvika, Norway
        • Ep0092 775
  • Poland
      • Katowice, Poland
        • Ep0092 605
      • Katowice, Poland
        • Ep0092 616
      • Kraków, Poland
        • Ep0092 603
      • Kraków, Poland
        • Ep0092 614
      • Lublin, Poland
        • Ep0092 610
      • Lublin, Poland
        • Ep0092 620
      • Nowa Sól, Poland
        • Ep0092 606
      • Warszawa, Poland
        • Ep0092 611
      • Wrocław, Poland
        • Ep0092 615
      • Zamość, Poland
        • Ep0092 619
      • Zgierz, Poland
        • Ep0092 618
      • Łódź, Poland
        • Ep0092 612
  • Portugal
      • Aveiro, Portugal
        • Ep0092 952
      • Matosinhos, Portugal
        • Ep0092 950
  • Romania
      • Bucuresti, Romania
        • Ep0092 925
      • Bucuresti, Romania
        • Ep0092 926
      • Târgu-Mureş, Romania
        • Ep0092 927
  • Serbia
      • Belgrade, Serbia
        • Ep0092 327
      • Novi Sad, Serbia
        • Ep0092 325
  • Slovakia
      • Bardejov, Slovakia
        • Ep0092 004
  • Spain
      • Alicante, Spain
        • Ep0092 662
      • Barcelona, Spain
        • Ep0092 651
      • Barcelona, Spain
        • Ep0092 652
      • Barcelona, Spain
        • Ep0092 658
      • Madrid, Spain
        • Ep0092 674
      • Valencia, Spain
        • Ep0092 657
      • Zaragoza, Spain
        • Ep0092 676
  • Sweden
      • Göteborg, Sweden
        • Ep0092 576
      • Linköping, Sweden
        • Ep0092 575
  • Switzerland
      • Zürich, Switzerland
        • Ep0092 053
  • Turkey
      • Ankara, Turkey
        • Ep0092 913
      • Antalya, Turkey
        • Ep0092 915
      • Istanbul, Turkey
        • Ep0092 900
      • Istanbul, Turkey
        • Ep0092 906
      • Istanbul, Turkey
        • Ep0092 909
      • Trabzon, Turkey
        • Ep0092 908
  • United Kingdom
      • Brighton, United Kingdom
        • Ep0092 766
      • Manchester, United Kingdom
        • Ep0092 750
      • Swansea, United Kingdom
        • Ep0092 764
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85226
        • Ep0092 839
      • Tucson, Arizona, United States, 85724
        • Ep0092 881
    • California
      • Carlsbad, California, United States, 92011
        • Ep0092 633
      • Orange, California, United States, 92868
        • Ep0092 629
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • Ep0092 845
    • Florida
      • Bradenton, Florida, United States, 34209
        • Ep0092 892
      • Hialeah, Florida, United States, 33016
        • Ep0092 640
      • Jacksonville, Florida, United States, 32209
        • Ep0092 641
      • Orlando, Florida, United States, 32806
        • Ep0092 823
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Ep0092 803
    • Illinois
      • Urbana, Illinois, United States, 61801
        • Ep0092 637
    • Indiana
      • Anderson, Indiana, United States, 46011
        • Ep0092 880
      • Fort Wayne, Indiana, United States, 46804
        • Ep0092 638
    • Iowa
      • Ames, Iowa, United States, 50010
        • Ep0092 630
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Ep0092 707
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Ep0092 822
      • Bethesda, Maryland, United States, 20817
        • Ep0092 818
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Ep0092 889
    • Minnesota
      • Golden Valley, Minnesota, United States, 55422
        • Ep0092 645
      • Minneapolis, Minnesota, United States, 55416
        • Ep0092 644
    • New York
      • Bronx, New York, United States, 10467
        • Ep0092 895
      • Brooklyn, New York, United States, 11203
        • Ep0092 878
      • New York, New York, United States, 10075
        • Ep0092 876
      • Syracuse, New York, United States, 13210
        • Ep0092 893
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Ep0092 890
      • Charlotte, North Carolina, United States, 28204
        • Ep0092 884
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ep0092 642
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73106
        • Ep0092 647
    • Oregon
      • Portland, Oregon, United States, 97225
        • Ep0092 882
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Ep0092 802
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Ep0092 829
    • Washington
      • Renton, Washington, United States, 98055
        • Ep0092 639

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Padsevonil dosing regimen 1
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Drug: Placebo
Placebo will be provided matching padsevonil.
Experimental: Padsevonil dosing regimen 2
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Drug: Placebo
Placebo will be provided matching padsevonil.
Experimental: Padsevonil dosing regimen 3
Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Drug: Placebo
Placebo will be provided matching padsevonil.
Placebo Comparator: Placebo
Subjects randomized to the placebo group will receive a combination of several placebo tablets to maintain the blinding.
Drug: Placebo
Placebo will be provided matching padsevonil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Log-transformed Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period
Time Frame: From 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.
From Baseline over the 12 Week Maintenance Period (up to Week 16)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: 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.
From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
Time Frame: 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.
From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame: 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.
From Baseline until Safety Follow-Up (up to Week 23)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
75% Responder Rate From Baseline Over the 12-week Maintenance Period
Time Frame: From 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.
From Baseline over the 12 Week Maintenance Period (up to Week 16)
50% Responder Rate From Baseline Over the 12-week Maintenance Period
Time Frame: From 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.
From Baseline over the 12 Week Maintenance Period (up to Week 16)
Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period
Time Frame: From 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.
From Baseline over the 12 Week Maintenance Period (up to Week 16)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UCB Biopharma SRL

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2019

Primary Completion (Actual)

September 28, 2020

Study Completion (Actual)

September 28, 2020

Study Registration Dates

First Submitted

November 9, 2018

First Submitted That Met QC Criteria

November 9, 2018

First Posted (Actual)

November 14, 2018

Study Record Updates

Last Update Posted (Estimate)

December 21, 2022

Last Update Submitted That Met QC Criteria

December 19, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP0092
  • 2018-002303-33 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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