Clinical trial NCT03739840: A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Drug-Resistant Epilepsy
Focal-Onset Seizures
Keywords: Epilepsy
Padsevonil
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2018-11-14
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Log-transformed Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period
timeFrame: From Baseline over the 12 Week Maintenance Period (up to Week 16)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From Baseline until Safety Follow-Up (up to Week 23)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
timeFrame: From Baseline until Safety Follow-Up (up to Week 23)
measure: Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: From Baseline until Safety Follow-Up (up to Week 23)
Secondary outcomes:
measure: 75% Responder Rate From Baseline Over the 12-week Maintenance Period
timeFrame: From Baseline over the 12 Week Maintenance Period (up to Week 16)
measure: 50% Responder Rate From Baseline Over the 12-week Maintenance Period
timeFrame: From Baseline over the 12 Week Maintenance Period (up to Week 16)
measure: Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period
timeFrame: From Baseline over the 12 Week Maintenance Period (up to Week 16)
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ep0092 839
state: Arizona
city: Tucson
country: United States
facility: Ep0092 881
state: Arizona
city: Carlsbad
country: United States
facility: Ep0092 633
state: California
city: Orange
country: United States
facility: Ep0092 629
state: California
city: Washington
country: United States
facility: Ep0092 845
state: District of Columbia
city: Bradenton
country: United States
facility: Ep0092 892
state: Florida
city: Hialeah
country: United States
facility: Ep0092 640
state: Florida
city: Jacksonville
country: United States
facility: Ep0092 641
state: Florida
city: Orlando
country: United States
facility: Ep0092 823
state: Florida
city: Honolulu
country: United States
facility: Ep0092 803
state: Hawaii
city: Urbana
country: United States
facility: Ep0092 637
state: Illinois
city: Anderson
country: United States
facility: Ep0092 880
state: Indiana
city: Fort Wayne
country: United States
facility: Ep0092 638
state: Indiana
city: Ames
country: United States
facility: Ep0092 630
state: Iowa
city: Lexington
country: United States
facility: Ep0092 707
state: Kentucky
city: Baltimore
country: United States
facility: Ep0092 822
state: Maryland
city: Bethesda
country: United States
facility: Ep0092 818
state: Maryland
city: Boston
country: United States
facility: Ep0092 889
state: Massachusetts
city: Golden Valley
country: United States
facility: Ep0092 645
state: Minnesota
city: Minneapolis
country: United States
facility: Ep0092 644
state: Minnesota
city: Bronx
country: United States
facility: Ep0092 895
state: New York
city: Brooklyn
country: United States
facility: Ep0092 878
state: New York
city: New York
country: United States
facility: Ep0092 876
state: New York
city: Syracuse
country: United States
facility: Ep0092 893
state: New York
city: Chapel Hill
country: United States
facility: Ep0092 890
state: North Carolina
city: Charlotte
country: United States
facility: Ep0092 884
state: North Carolina
city: Columbus
country: United States
facility: Ep0092 642
state: Ohio
city: Oklahoma City
country: United States
facility: Ep0092 647
state: Oklahoma
city: Portland
country: United States
facility: Ep0092 882
state: Oregon
city: Philadelphia
country: United States
facility: Ep0092 802
state: Pennsylvania
city: Charlottesville
country: United States
facility: Ep0092 829
state: Virginia
city: Renton
country: United States
facility: Ep0092 639
state: Washington
city: Box Hill
country: Australia
facility: Ep0092 855
city: Camperdown
country: Australia
facility: Ep0092 861
city: Fitzroy
country: Australia
facility: Ep0092 850
city: Heidelberg
country: Australia
facility: Ep0092 853
city: Melbourne
country: Australia
facility: Ep0092 852
city: Brussels
country: Belgium
facility: Ep0092 109
city: Ottignies
country: Belgium
facility: Ep0092 107
city: Bihać
country: Bosnia and Herzegovina
facility: Ep0092 080
city: Mostar
country: Bosnia and Herzegovina
facility: Ep0092 077
city: Sarajevo
country: Bosnia and Herzegovina
facility: Ep0092 075
city: Tuzla
country: Bosnia and Herzegovina
facility: Ep0092 082
city: Blagoevgrad
country: Bulgaria
facility: Ep0092 150
city: Pleven
country: Bulgaria
facility: Ep0092 151
city: Pleven
country: Bulgaria
facility: Ep0092 156
city: Sofia
country: Bulgaria
facility: Ep0092 154
city: Zagreb
country: Croatia
facility: Ep0092 125
city: Zagreb
country: Croatia
facility: Ep0092 126
city: Zagreb
country: Croatia
facility: Ep0092 127
city: Zagreb
country: Croatia
facility: Ep0092 128
city: Brno
country: Czechia
facility: Ep0092 254
city: Ostrava
country: Czechia
facility: Ep0092 258
city: Praha 5
country: Czechia
facility: Ep0092 250
city: Praha 6
country: Czechia
facility: Ep0092 251
city: Aarhus
country: Denmark
facility: Ep0092 016
city: Odense
country: Denmark
facility: Ep0092 015
city: Tallinn
country: Estonia
facility: Ep0092 276
city: Tallinn
country: Estonia
facility: Ep0092 277
city: Tartu
country: Estonia
facility: Ep0092 275
city: Tampere
country: Finland
facility: Ep0092 027
city: Lyon
country: France
facility: Ep0092 312
city: Paris
country: France
facility: Ep0092 310
city: Strasbourg
country: France
facility: Ep0092 301
city: Berlin
country: Germany
facility: Ep0092 365
city: Bernau
country: Germany
facility: Ep0092 362
city: Bielefeld
country: Germany
facility: Ep0092 363
city: Frankfurt
country: Germany
facility: Ep0092 350
city: Jena
country: Germany
facility: Ep0092 368
city: Leipzig
country: Germany
facility: Ep0092 357
city: Regensburg
country: Germany
facility: Ep0092 376
city: Ioánnina
country: Greece
facility: Ep0092 425
city: Thessaloníki
country: Greece
facility: Ep0092 426
city: Thessaloníki
country: Greece
facility: Ep0092 427
city: Thessaloníki
country: Greece
facility: Ep0092 428
city: Budapest
country: Hungary
facility: Ep0092 403
city: Debrecen
country: Hungary
facility: Ep0092 405
city: Pécs
country: Hungary
facility: Ep0092 404
city: Cork
country: Ireland
facility: Ep0092 035
city: Dublin
country: Ireland
facility: Ep0092 036
city: Milano
country: Italy
facility: Ep0092 452
city: Asahikawa
country: Japan
facility: Ep0092 526
city: Asaka
country: Japan
facility: Ep0092 501
city: Bunkyō-Ku
country: Japan
facility: Ep0092 521
city: Bunkyō-Ku
country: Japan
facility: Ep0092 525
city: Hamamatsu
country: Japan
facility: Ep0092 504
city: Hiroshima
country: Japan
facility: Ep0092 505
city: Hōfu
country: Japan
facility: Ep0092 513
city: Itami
country: Japan
facility: Ep0092 507
city: Izumi
country: Japan
facility: Ep0092 531
city: Kumamoto
country: Japan
facility: Ep0092 539
city: Kure
country: Japan
facility: Ep0092 533
city: Kyoto
country: Japan
facility: Ep0092 514
city: Nagakute
country: Japan
facility: Ep0092 512
city: Saitama
country: Japan
facility: Ep0092 515
city: Sapporo
country: Japan
facility: Ep0092 508
city: Shinagawa-Ku
country: Japan
facility: Ep0092 527
city: Shizuoka
country: Japan
facility: Ep0092 509
city: Yonago
country: Japan
facility: Ep0092 529
city: Ōmura
country: Japan
facility: Ep0092 522
city: Ōsaka-sayama
country: Japan
facility: Ep0092 530
city: Sandvika
country: Norway
facility: Ep0092 775
city: Katowice
country: Poland
facility: Ep0092 605
city: Katowice
country: Poland
facility: Ep0092 616
city: Kraków
country: Poland
facility: Ep0092 603
city: Kraków
country: Poland
facility: Ep0092 614
city: Lublin
country: Poland
facility: Ep0092 610
city: Lublin
country: Poland
facility: Ep0092 620
city: Nowa Sól
country: Poland
facility: Ep0092 606
city: Warszawa
country: Poland
facility: Ep0092 611
city: Wrocław
country: Poland
facility: Ep0092 615
city: Zamość
country: Poland
facility: Ep0092 619
city: Zgierz
country: Poland
facility: Ep0092 618
city: Łódź
country: Poland
facility: Ep0092 612
city: Aveiro
country: Portugal
facility: Ep0092 952
city: Matosinhos
country: Portugal
facility: Ep0092 950
city: Bucuresti
country: Romania
facility: Ep0092 925
city: Bucuresti
country: Romania
facility: Ep0092 926
city: Târgu-Mureş
country: Romania
facility: Ep0092 927
city: Belgrade
country: Serbia
facility: Ep0092 327
city: Novi Sad
country: Serbia
facility: Ep0092 325
city: Bardejov
country: Slovakia
facility: Ep0092 004
city: Alicante
country: Spain
facility: Ep0092 662
city: Barcelona
country: Spain
facility: Ep0092 651
city: Barcelona
country: Spain
facility: Ep0092 652
city: Barcelona
country: Spain
facility: Ep0092 658
city: Madrid
country: Spain
facility: Ep0092 674
city: Valencia
country: Spain
facility: Ep0092 657
city: Zaragoza
country: Spain
facility: Ep0092 676
city: Göteborg
country: Sweden
facility: Ep0092 576
city: Linköping
country: Sweden
facility: Ep0092 575
city: Zürich
country: Switzerland
facility: Ep0092 053
city: Ankara
country: Turkey
facility: Ep0092 913
city: Antalya
country: Turkey
facility: Ep0092 915
city: Istanbul
country: Turkey
facility: Ep0092 900
city: Istanbul
country: Turkey
facility: Ep0092 906
city: Istanbul
country: Turkey
facility: Ep0092 909
city: Trabzon
country: Turkey
facility: Ep0092 908
city: Brighton
country: United Kingdom
facility: Ep0092 766
city: Manchester
country: United Kingdom
facility: Ep0092 750
city: Swansea
country: United Kingdom
facility: Ep0092 764
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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.