Clinical trial NCT03373383: Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose Finding 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: COMPLETED
Phase: PHASE2
Conditions: Drug-resistant Epilepsy
Focal-Onset Seizures
Keywords: Epilepsy
Padsevonil
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2017-12-14
Enrollment: 411
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 characterize the dose-response relationship with respect to efficacy of Padsevonil administered concomitantly with up to 3 anti-epileptic drugs (AEDs) 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
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject and/or Caregiver or Observed by the Investigator During the Entire Study
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) During the Entire Study
timeFrame: From Baseline until Safety Follow-Up (up to Week 23)
Secondary outcomes:
measure: 75 % Responder Rate Over the 12 Week Maintenance Period
timeFrame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
measure: 50 % Responder Rate Over the 12 Week Maintenance Period
timeFrame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
measure: Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
timeFrame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ep0091 839
state: Arizona
city: Little Rock
country: United States
facility: Ep0091 810
state: Arkansas
city: La Jolla
country: United States
facility: Ep0091 815
state: California
city: San Francisco
country: United States
facility: Ep0091 801
state: California
city: Washington
country: United States
facility: Ep0091 845
state: District of Columbia
city: Ocala
country: United States
facility: Ep0091 809
state: Florida
city: Orlando
country: United States
facility: Ep0091 823
state: Florida
city: Port Charlotte
country: United States
facility: Ep0091 825
state: Florida
city: Tallahassee
country: United States
facility: Ep0091 820
state: Florida
city: Atlanta
country: United States
facility: Ep0091 873
state: Georgia
city: Honolulu
country: United States
facility: Ep0091 803
state: Hawaii
city: Peoria
country: United States
facility: Ep0091 832
state: Illinois
city: Baltimore
country: United States
facility: Ep0091 822
state: Maryland
city: Bethesda
country: United States
facility: Ep0091 818
state: Maryland
city: Saint Paul
country: United States
facility: Ep0091 817
state: Minnesota
city: Hackensack
country: United States
facility: Ep0091 806
state: New Jersey
city: New York
country: United States
facility: Ep0091 827
state: New York
city: Philadelphia
country: United States
facility: Ep0091 800
state: Pennsylvania
city: Philadelphia
country: United States
facility: Ep0091 802
state: Pennsylvania
city: Cordova
country: United States
facility: Ep0091 838
state: Tennessee
city: Nashville
country: United States
facility: Ep0091 835
state: Tennessee
city: Austin
country: United States
facility: Ep0091 805
state: Texas
city: Austin
country: United States
facility: Ep0091 844
state: Texas
city: Dallas
country: United States
facility: Ep0091 836
state: Texas
city: Dallas
country: United States
facility: Ep0091 830
state: Texas
city: Round Rock
country: United States
facility: Ep0091 824
state: Texas
city: San Antonio
country: United States
facility: Ep0091 870
state: Texas
city: Box Hill
country: Australia
facility: Ep0091 855
city: Clayton
country: Australia
facility: Ep0091 857
city: Fitzroy
country: Australia
facility: Ep0091 850
city: Herston
country: Australia
facility: Ep0091 859
city: Melbourne
country: Australia
facility: Ep0091 852
city: Melbourne
country: Australia
facility: Ep0091 853
city: Randwick
country: Australia
facility: Ep0091 856
city: Westmead
country: Australia
facility: Ep0091 854
city: Brugge
country: Belgium
facility: Ep0091 102
city: Brussels
country: Belgium
facility: Ep0091 101
city: Gent
country: Belgium
facility: Ep0091 105
city: Leuven
country: Belgium
facility: Ep0091 100
city: Blagoevgrad
country: Bulgaria
facility: Ep0091 150
city: Pleven
country: Bulgaria
facility: Ep0091 151
city: Pleven
country: Bulgaria
facility: Ep0091 153
city: Sofia
country: Bulgaria
facility: Ep0091 152
city: Sofia
country: Bulgaria
facility: Ep0091 154
city: Sofia
country: Bulgaria
facility: Ep0091 155
city: Greenfield Park
country: Canada
facility: Ep0091 200
city: London
country: Canada
facility: Ep0091 205
city: Montréal
country: Canada
facility: Ep0091 201
city: Brno
country: Czechia
facility: Ep0091 254
city: Ostrava-Poruba
country: Czechia
facility: Ep0091 255
city: Praha 4
country: Czechia
facility: Ep0091 252
city: Praha 5
country: Czechia
facility: Ep0091 250
city: Praha 8
country: Czechia
facility: Ep0091 253
city: Praha
country: Czechia
facility: Ep0091 251
city: Clermont-Ferrand Cedex 1
country: France
facility: Ep0091 307
city: Dijon
country: France
facility: Ep0091 309
city: Lille
country: France
facility: Ep0091 300
city: Montpellier
country: France
facility: Ep0091 302
city: Paris
country: France
facility: Ep0091 305
city: Rennes
country: France
facility: Ep0091 303
city: Toulouse Cedex 9
country: France
facility: Ep0091 306
city: Bad Neustadt An Der Saale
country: Germany
facility: Ep0091 361
city: Berlin
country: Germany
facility: Ep0091 365
city: Bernau
country: Germany
facility: Ep0091 362
city: Bielefeld
country: Germany
facility: Ep0091 363
city: Bonn
country: Germany
facility: Ep0091 358
city: Frankfurt am main
country: Germany
facility: Ep0091 350
city: Freiburg
country: Germany
facility: Ep0091 360
city: Hamburg
country: Germany
facility: Ep0091 364
city: Jena
country: Germany
facility: Ep0091 368
city: Kork
country: Germany
facility: Ep0091 366
city: Leipzig
country: Germany
facility: Ep0091 357
city: Marburg
country: Germany
facility: Ep0091 353
city: München
country: Germany
facility: Ep0091 354
city: Münster
country: Germany
facility: Ep0091 351
city: Osnabrück
country: Germany
facility: Ep0091 356
city: Ravensburg
country: Germany
facility: Ep0091 367
city: Strausberg
country: Germany
facility: Ep0091 301
city: Tübingen
country: Germany
facility: Ep0091 352
city: Budapest
country: Hungary
facility: Ep0091 400
city: Budapest
country: Hungary
facility: Ep0091 403
city: Debrecen
country: Hungary
facility: Ep0091 402
city: Bologna
country: Italy
facility: Ep0091 462
city: Cagliari
country: Italy
facility: Ep0091 450
city: Foggia
country: Italy
facility: Ep0091 461
city: Milano
country: Italy
facility: Ep0091 452
city: Pavia
country: Italy
facility: Ep0091 459
city: Perugia
country: Italy
facility: Ep0091 453
city: Pozzilli
country: Italy
facility: Ep0091 458
city: Reggio Calabria
country: Italy
facility: Ep0091 454
city: Roma
country: Italy
facility: Ep0091 455
city: Roma
country: Italy
facility: Ep0091 457
city: Roma
country: Italy
facility: Ep0091 460
city: Asaka
country: Japan
facility: Ep0091 501
city: Fukuoka
country: Japan
facility: Ep0091 511
city: Hiroshima
country: Japan
facility: Ep0091 505
city: Hōfu
country: Japan
facility: Ep0091 513
city: Itami
country: Japan
facility: Ep0091 507
city: Kodaira
country: Japan
facility: Ep0091 503
city: Kyoto
country: Japan
facility: Ep0091 514
city: Nagakute
country: Japan
facility: Ep0091 512
city: Niigata
country: Japan
facility: Ep0091 510
city: Saitama
country: Japan
facility: Ep0091 515
city: Shizuoka
country: Japan
facility: Ep0091 509
city: Kaunas
country: Lithuania
facility: Ep0091 703
city: Vilnius
country: Lithuania
facility: Ep0091 701
city: Vilnius
country: Lithuania
facility: Ep0091 702
city: Culiacán
country: Mexico
facility: Ep0091 553
city: Mexico Distrito Federal
country: Mexico
facility: Ep0091 552
city: Gdańsk
country: Poland
facility: Ep0091 601
city: Grodzisk Mazowiecki
country: Poland
facility: Ep0091 607
city: Katowice
country: Poland
facility: Ep0091 605
city: Katowice
country: Poland
facility: Ep0091 608
city: Kraków
country: Poland
facility: Ep0091 603
city: Lublin
country: Poland
facility: Ep0091 604
city: Nowa Sól
country: Poland
facility: Ep0091 606
city: Poznań
country: Poland
facility: Ep0091 600
city: Poznań
country: Poland
facility: Ep0091 609
city: Świdnik
country: Poland
facility: Ep0091 602
city: Santa Maria Da Feira
country: Portugal
facility: Ep0091 952
city: Bardejov
country: Slovakia
facility: Ep0091 004
city: Hlohovec
country: Slovakia
facility: Ep0091 001
city: Alicante
country: Spain
facility: Ep0091 662
city: Barcelona
country: Spain
facility: Ep0091 651
city: Barcelona
country: Spain
facility: Ep0091 652
city: Barcelona
country: Spain
facility: Ep0091 658
city: Barcelona
country: Spain
facility: Ep0091 664
city: Bilbao
country: Spain
facility: Ep0091 668
city: Córdoba
country: Spain
facility: Ep0091 666
city: Madrid
country: Spain
facility: Ep0091 650
city: Madrid
country: Spain
facility: Ep0091 656
city: Madrid
country: Spain
facility: Ep0091 660
city: Madrid
country: Spain
facility: Ep0091 661
city: Málaga
country: Spain
facility: Ep0091 659
city: Sevilla
country: Spain
facility: Ep0091 663
city: Terrassa
country: Spain
facility: Ep0091 665
city: Valencia
country: Spain
facility: Ep0091 657
city: Valencia
country: Spain
facility: Ep0091 667
city: Valladolid
country: Spain
facility: Ep0091 653
city: Eskişehir
country: Turkey
facility: Ep0091 904
city: Istanbul
country: Turkey
facility: Ep0091 900
city: Istanbul
country: Turkey
facility: Ep0091 901
city: Birmingham
country: United Kingdom
facility: Ep0091 752
city: Cardiff
country: United Kingdom
facility: Ep0091 751
city: Inverness
country: United Kingdom
facility: Ep0091 756
city: London
country: United Kingdom
facility: Ep0091 757
city: Manchester
country: United Kingdom
facility: Ep0091 750
city: Swansea
country: United Kingdom
facility: Ep0091 753
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.
citation: Kramer H, Bicer C, Otoul C, Rospo C, Macpherson M, Watling M, Bani M, Sciberras D, Chanteux H. Clinical Bridging Studies and Modeling Approach for Implementation of a Patient Centric Sampling Technique in Padsevonil Clinical Development. AAPS J. 2023 Nov 16;26(1):1. doi: 10.1208/s12248-023-00866-7.