Study Stopped
Based on available data, UCB has decided to stop development of padsevonil as adjunctive treatment of focal-onset seizure
A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy
DUET
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
2 other identifiers
interventional
232
26 countries
136
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Mar 2019
136 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2018
CompletedFirst Posted
Study publicly available on registry
November 14, 2018
CompletedStudy Start
First participant enrolled
March 6, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 28, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
September 28, 2020
CompletedResults Posted
Study results publicly available
October 25, 2021
CompletedDecember 21, 2022
December 1, 2022
1.6 years
November 9, 2018
September 24, 2021
December 19, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Change in Log-transformed Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period
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)
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
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)
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 Outcomes (3)
75% Responder Rate 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
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
From Baseline over the 12 Week Maintenance Period (up to Week 16)
Study Arms (4)
Padsevonil dosing regimen 1
EXPERIMENTALSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Padsevonil dosing regimen 2
EXPERIMENTALSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Padsevonil dosing regimen 3
EXPERIMENTALSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Placebo
PLACEBO COMPARATORSubjects randomized to the placebo group will receive a combination of several placebo tablets to maintain the blinding.
Interventions
Padsevonil in different dosages.
Placebo will be provided matching padsevonil.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (141)
Ep0092 839
Chandler, Arizona, 85226, United States
Ep0092 881
Tucson, Arizona, 85724, United States
Ep0092 633
Carlsbad, California, 92011, United States
Ep0092 629
Orange, California, 92868, United States
Ep0092 845
Washington D.C., District of Columbia, 20037, United States
Ep0092 892
Bradenton, Florida, 34209, United States
Ep0092 640
Hialeah, Florida, 33016, United States
Ep0092 641
Jacksonville, Florida, 32209, United States
Ep0092 823
Orlando, Florida, 32806, United States
Ep0092 803
Honolulu, Hawaii, 96817, United States
Ep0092 637
Urbana, Illinois, 61801, United States
Ep0092 880
Anderson, Indiana, 46011, United States
Ep0092 638
Fort Wayne, Indiana, 46804, United States
Ep0092 630
Ames, Iowa, 50010, United States
Ep0092 707
Lexington, Kentucky, 40536, United States
Ep0092 822
Baltimore, Maryland, 21287, United States
Ep0092 818
Bethesda, Maryland, 20817, United States
Ep0092 889
Boston, Massachusetts, 02215, United States
Ep0092 645
Golden Valley, Minnesota, 55422, United States
Ep0092 644
Minneapolis, Minnesota, 55416, United States
Ep0092 878
Brooklyn, New York, 11203, United States
Ep0092 876
New York, New York, 10075, United States
Ep0092 893
Syracuse, New York, 13210, United States
Ep0092 895
The Bronx, New York, 10467, United States
Ep0092 890
Chapel Hill, North Carolina, 27599, United States
Ep0092 884
Charlotte, North Carolina, 28204, United States
Ep0092 642
Columbus, Ohio, 43210, United States
Ep0092 647
Oklahoma City, Oklahoma, 73106, United States
Ep0092 882
Portland, Oregon, 97225, United States
Ep0092 802
Philadelphia, Pennsylvania, 19107, United States
Ep0092 829
Charlottesville, Virginia, 22903, United States
Ep0092 639
Renton, Washington, 98055, United States
Ep0092 855
Box Hill, Australia
Ep0092 861
Camperdown, Australia
Ep0092 850
Fitzroy, Australia
Ep0092 853
Heidelberg, Australia
Ep0092 852
Melbourne, Australia
Ep0092 109
Brussels, Belgium
Ep0092 107
Ottignies, Belgium
Ep0092 080
Bihać, Bosnia and Herzegovina
Ep0092 077
Mostar, Bosnia and Herzegovina
Ep0092 075
Sarajevo, Bosnia and Herzegovina
Ep0092 082
Tuzla, Bosnia and Herzegovina
Ep0092 150
Blagoevgrad, Bulgaria
Ep0092 151
Pleven, Bulgaria
Ep0092 156
Pleven, Bulgaria
Ep0092 154
Sofia, Bulgaria
Ep0092 125
Zagreb, Croatia
Ep0092 126
Zagreb, Croatia
Ep0092 127
Zagreb, Croatia
Ep0092 128
Zagreb, Croatia
Ep0092 254
Brno, Czechia
Ep0092 258
Ostrava, Czechia
Ep0092 250
Prague, Czechia
Ep0092 251
Prague, Czechia
Ep0092 016
Aarhus, Denmark
Ep0092 015
Odense, Denmark
Ep0092 276
Tallinn, Estonia
Ep0092 277
Tallinn, Estonia
Ep0092 275
Tartu, Estonia
Ep0092 027
Tampere, Finland
Ep0092 312
Lyon, France
Ep0092 310
Paris, France
Ep0092 301
Strasbourg, France
Ep0092 365
Berlin, Germany
Ep0092 362
Bernau, Germany
Ep0092 363
Bielefeld, Germany
Ep0092 350
Frankfurt, Germany
Ep0092 368
Jena, Germany
Ep0092 357
Leipzig, Germany
Ep0092 376
Regensburg, Germany
Ep0092 425
Ioannina, Greece
Ep0092 426
Thessaloniki, Greece
Ep0092 427
Thessaloniki, Greece
Ep0092 428
Thessaloniki, Greece
Ep0092 403
Budapest, Hungary
Ep0092 405
Debrecen, Hungary
Ep0092 404
Pécs, Hungary
Ep0092 035
Cork, Ireland
Ep0092 036
Dublin, Ireland
Ep0092 452
Milan, Italy
Ep0092 526
Asahikawa, Japan
Ep0092 501
Asaka, Japan
Ep0092 521
Bunkyō City, Japan
Ep0092 525
Bunkyō City, Japan
Ep0092 504
Hamamatsu, Japan
Ep0092 505
Hiroshima, Japan
Ep0092 513
Hōfu, Japan
Ep0092 507
Itami, Japan
Ep0092 531
Izumi, Japan
Ep0092 539
Kumamoto, Japan
Ep0092 533
Kure, Japan
Ep0092 514
Kyoto, Japan
Ep0092 512
Nagakute, Japan
Ep0092 522
Ōmura, Japan
Ep0092 530
Ōsaka-sayama, Japan
Ep0092 515
Saitama, Japan
Ep0092 508
Sapporo, Japan
Ep0092 527
Shinagawa-Ku, Japan
Ep0092 509
Shizuoka, Japan
Ep0092 529
Yonago, Japan
Ep0092 775
Sandvika, Norway
Ep0092 605
Katowice, Poland
Ep0092 616
Katowice, Poland
Ep0092 603
Krakow, Poland
Ep0092 614
Krakow, Poland
Ep0092 612
Lodz, Poland
Ep0092 610
Lublin, Poland
Ep0092 620
Lublin, Poland
Ep0092 606
Nowa Sól, Poland
Ep0092 611
Warsaw, Poland
Ep0092 615
Wroclaw, Poland
Ep0092 619
Zamość, Poland
Ep0092 618
Zgierz, Poland
Ep0092 952
Aveiro, Portugal
Ep0092 950
Matosinhos Municipality, Portugal
Ep0092 925
Bucharest, Romania
Ep0092 926
Bucharest, Romania
Ep0092 927
Târgu Mureş, Romania
Ep0092 327
Belgrade, Serbia
Ep0092 325
Novi Sad, Serbia
Ep0092 004
Bardejov, Slovakia
Ep0092 662
Alicante, Spain
Ep0092 651
Barcelona, Spain
Ep0092 652
Barcelona, Spain
Ep0092 658
Barcelona, Spain
Ep0092 674
Madrid, Spain
Ep0092 657
Valencia, Spain
Ep0092 676
Zaragoza, Spain
Ep0092 576
Gothenburg, Sweden
Ep0092 575
Linköping, Sweden
Ep0092 053
Zurich, Switzerland
Ep0092 913
Ankara, Turkey (Türkiye)
Ep0092 915
Antalya, Turkey (Türkiye)
Ep0092 900
Istanbul, Turkey (Türkiye)
Ep0092 906
Istanbul, Turkey (Türkiye)
Ep0092 909
Istanbul, Turkey (Türkiye)
Ep0092 908
Trabzon, Turkey (Türkiye)
Ep0092 766
Brighton, United Kingdom
Ep0092 750
Manchester, United Kingdom
Ep0092 764
Swansea, United Kingdom
Related Publications (1)
Rademacher M, Toledo M, Van Paesschen W, Liow KK, Milanov IG, Esch ML, Wang N, MacPherson M, Byrnes WJ, Minh TDC, Webster E, Werhahn KJ. Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials. Epilepsia Open. 2022 Dec;7(4):758-770. doi: 10.1002/epi4.12656. Epub 2022 Oct 22.
PMID: 36176044RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- UCB
- Organization
- Cares
Study Officials
- STUDY DIRECTOR
UCB Cares
001 844 599 2273 (UCB)
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2018
First Posted
November 14, 2018
Study Start
March 6, 2019
Primary Completion
September 28, 2020
Study Completion
September 28, 2020
Last Updated
December 21, 2022
Results First Posted
October 25, 2021
Record last verified: 2022-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- 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.
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.