A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy
- Conditions
- Drug-Resistant EpilepsyFocal-Onset Seizures
- Interventions
- Drug: PadsevonilDrug: 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
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Padsevonil dosing regimen 1 Placebo Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding. Padsevonil dosing regimen 2 Placebo Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding. Placebo Placebo Subjects randomized to the placebo group will receive a combination of several placebo tablets to maintain the blinding. Padsevonil dosing regimen 3 Placebo Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding. Padsevonil dosing regimen 2 Padsevonil Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding. Padsevonil dosing regimen 3 Padsevonil Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding. Padsevonil dosing regimen 1 Padsevonil Subjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
- Primary Outcome Measures
Name Time Method 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 Period 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.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal 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.
- Secondary Outcome Measures
Name Time Method 75% Responder Rate From Baseline Over the 12-week Maintenance Period 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.
50% Responder Rate From Baseline Over the 12-week Maintenance Period 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.
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) 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)
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🇧🇬Blagoevgrad, Bulgaria
Ep0092 128
🇭🇷Zagreb, Croatia
Ep0092 276
🇪🇪Tallinn, Estonia
Ep0092 277
🇪🇪Tallinn, Estonia
Ep0092 053
🇨🇭Zürich, Switzerland
Ep0092 275
🇪🇪Tartu, Estonia
Ep0092 427
🇬🇷Thessaloníki, Greece
Ep0092 404
🇭🇺Pécs, Hungary
Ep0092 508
🇯🇵Sapporo, Japan
Ep0092 610
🇵🇱Lublin, Poland
Ep0092 504
🇯🇵Hamamatsu, Japan
Ep0092 505
🇯🇵Hiroshima, Japan
Ep0092 539
🇯🇵Kumamoto, Japan
Ep0092 512
🇯🇵Nagakute, Japan
Ep0092 522
🇯🇵Ōmura, Japan
Ep0092 530
🇯🇵Ōsaka-sayama, Japan
Ep0092 926
🇷🇴Bucuresti, Romania
Ep0092 845
🇺🇸Washington, District of Columbia, United States
Ep0092 637
🇺🇸Urbana, Illinois, United States
Ep0092 645
🇺🇸Golden Valley, Minnesota, United States
Ep0092 878
🇺🇸Brooklyn, New York, United States
Ep0092 080
🇧🇦Bihać, Bosnia and Herzegovina
Ep0092 077
🇧🇦Mostar, Bosnia and Herzegovina
Ep0092 154
🇧🇬Sofia, Bulgaria
Ep0092 127
🇭🇷Zagreb, Croatia
Ep0092 016
🇩🇰Aarhus, Denmark
Ep0092 312
🇫🇷Lyon, France
Ep0092 151
🇧🇬Pleven, Bulgaria
Ep0092 125
🇭🇷Zagreb, Croatia
Ep0092 015
🇩🇰Odense, Denmark
Ep0092 350
🇩🇪Frankfurt, Germany
Ep0092 363
🇩🇪Bielefeld, Germany
Ep0092 254
🇨🇿Brno, Czechia
Ep0092 376
🇩🇪Regensburg, Germany
Ep0092 853
🇦🇺Heidelberg, Australia
Ep0092 893
🇺🇸Syracuse, New York, United States
Ep0092 861
🇦🇺Camperdown, Australia
Ep0092 075
🇧🇦Sarajevo, Bosnia and Herzegovina
Ep0092 082
🇧🇦Tuzla, Bosnia and Herzegovina
Ep0092 126
🇭🇷Zagreb, Croatia
Ep0092 852
🇦🇺Melbourne, Australia
Ep0092 251
🇨🇿Praha 6, Czechia
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🇺🇸New York, New York, United States
Ep0092 156
🇧🇬Pleven, Bulgaria
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🇬🇷Thessaloníki, Greece
Ep0092 405
🇭🇺Debrecen, Hungary
Ep0092 501
🇯🇵Asaka, Japan
Ep0092 521
🇯🇵Bunkyō-Ku, Japan
Ep0092 884
🇺🇸Charlotte, North Carolina, United States
Ep0092 829
🇺🇸Charlottesville, Virginia, United States
Ep0092 639
🇺🇸Renton, Washington, United States
Ep0092 310
🇫🇷Paris, France
Ep0092 403
🇭🇺Budapest, Hungary
Ep0092 850
🇦🇺Fitzroy, Australia
Ep0092 365
🇩🇪Berlin, Germany
Ep0092 109
🇧🇪Brussels, Belgium
Ep0092 107
🇧🇪Ottignies, Belgium
Ep0092 362
🇩🇪Bernau, Germany
Ep0092 357
🇩🇪Leipzig, Germany
Ep0092 250
🇨🇿Praha 5, Czechia
Ep0092 855
🇦🇺Box Hill, Australia
Ep0092 258
🇨🇿Ostrava, Czechia
Ep0092 892
🇺🇸Bradenton, Florida, United States
Ep0092 642
🇺🇸Columbus, Ohio, United States
Ep0092 802
🇺🇸Philadelphia, Pennsylvania, United States
Ep0092 531
🇯🇵Izumi, Japan
Ep0092 881
🇺🇸Tucson, Arizona, United States
Ep0092 839
🇺🇸Chandler, Arizona, United States
Ep0092 633
🇺🇸Carlsbad, California, United States
Ep0092 629
🇺🇸Orange, California, United States
Ep0092 641
🇺🇸Jacksonville, Florida, United States
Ep0092 640
🇺🇸Hialeah, Florida, United States
Ep0092 880
🇺🇸Anderson, Indiana, United States
Ep0092 822
🇺🇸Baltimore, Maryland, United States
Ep0092 638
🇺🇸Fort Wayne, Indiana, United States
Ep0092 630
🇺🇸Ames, Iowa, United States
Ep0092 889
🇺🇸Boston, Massachusetts, United States
Ep0092 027
🇫🇮Tampere, Finland
Ep0092 301
🇫🇷Strasbourg, France
Ep0092 368
🇩🇪Jena, Germany
Ep0092 425
🇬🇷Ioánnina, Greece
Ep0092 428
🇬🇷Thessaloníki, Greece
Ep0092 035
🇮🇪Cork, Ireland
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🇮🇪Dublin, Ireland
Ep0092 452
🇮🇹Milano, Italy
Ep0092 526
🇯🇵Asahikawa, Japan
Ep0092 525
🇯🇵Bunkyō-Ku, Japan
Ep0092 513
🇯🇵Hōfu, Japan
Ep0092 507
🇯🇵Itami, Japan
Ep0092 533
🇯🇵Kure, Japan
Ep0092 514
🇯🇵Kyoto, Japan
Ep0092 515
🇯🇵Saitama, 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
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🇵🇱Kraków, Poland
Ep0092 614
🇵🇱Kraków, Poland
Ep0092 620
🇵🇱Lublin, Poland
Ep0092 606
🇵🇱Nowa Sól, Poland
Ep0092 611
🇵🇱Warszawa, Poland
Ep0092 615
🇵🇱Wrocław, Poland
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🇵🇱Zamość, Poland
Ep0092 618
🇵🇱Zgierz, Poland
Ep0092 612
🇵🇱Łódź, Poland
Ep0092 952
🇵🇹Aveiro, Portugal
Ep0092 950
🇵🇹Matosinhos, Portugal
Ep0092 925
🇷🇴Bucuresti, Romania
Ep0092 927
🇷🇴Târgu-Mureş, Romania
Ep0092 325
🇷🇸Novi Sad, Serbia
Ep0092 004
🇸🇰Bardejov, Slovakia
Ep0092 327
🇷🇸Belgrade, Serbia
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 576
🇸🇪Göteborg, Sweden
Ep0092 915
🇹🇷Antalya, Turkey
Ep0092 913
🇹🇷Ankara, Turkey
Ep0092 906
🇹🇷Istanbul, Turkey
Ep0092 900
🇹🇷Istanbul, Turkey
Ep0092 909
🇹🇷Istanbul, Turkey
Ep0092 750
🇬🇧Manchester, United Kingdom
Ep0092 908
🇹🇷Trabzon, Turkey
Ep0092 766
🇬🇧Brighton, United Kingdom
Ep0092 764
🇬🇧Swansea, United Kingdom
Ep0092 575
🇸🇪Linköping, Sweden
Ep0092 676
🇪🇸Zaragoza, Spain
Ep0092 818
🇺🇸Bethesda, Maryland, United States
Ep0092 882
🇺🇸Portland, Oregon, United States
Ep0092 647
🇺🇸Oklahoma City, Oklahoma, United States
Ep0092 644
🇺🇸Minneapolis, Minnesota, United States
Ep0092 823
🇺🇸Orlando, Florida, United States
Ep0092 803
🇺🇸Honolulu, Hawaii, United States
Ep0092 707
🇺🇸Lexington, Kentucky, United States
Ep0092 895
🇺🇸Bronx, New York, United States
Ep0092 890
🇺🇸Chapel Hill, North Carolina, United States