Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy
ARISE
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
2 other identifiers
interventional
411
19 countries
148
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2018
148 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
December 7, 2017
CompletedFirst Posted
Study publicly available on registry
December 14, 2017
CompletedStudy Start
First participant enrolled
February 12, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2020
CompletedResults Posted
Study results publicly available
April 9, 2021
CompletedDecember 19, 2023
December 1, 2023
2 years
December 7, 2017
January 28, 2021
December 15, 2023
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, 28-day adjusted 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
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
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.
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.
From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study
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 an 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.
From Baseline until Safety Follow-Up (up to Week 23)
Secondary Outcomes (3)
75 % Responder Rate Over the 12 Week Maintenance Period
End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
50 % Responder Rate Over the 12 Week Maintenance Period
End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Study Arms (5)
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.
Padsevonil dosing regimen 4
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 (148)
Ep0091 839
Chandler, Arizona, 85226, United States
Ep0091 810
Little Rock, Arkansas, 72205, United States
Ep0091 815
La Jolla, California, 92037, United States
Ep0091 801
San Francisco, California, 94115, United States
Ep0091 845
Washington D.C., District of Columbia, 20037, United States
Ep0091 809
Ocala, Florida, 34471, United States
Ep0091 823
Orlando, Florida, 32806, United States
Ep0091 825
Port Charlotte, Florida, 33952, United States
Ep0091 820
Tallahassee, Florida, 32308, United States
Ep0091 873
Atlanta, Georgia, 30303, United States
Ep0091 803
Honolulu, Hawaii, 96817, United States
Ep0091 832
Peoria, Illinois, 61637, United States
Ep0091 822
Baltimore, Maryland, 21287, United States
Ep0091 818
Bethesda, Maryland, 20817, United States
Ep0091 817
Saint Paul, Minnesota, 55102, United States
Ep0091 806
Hackensack, New Jersey, 07601, United States
Ep0091 827
New York, New York, 10016-48, United States
Ep0091 800
Philadelphia, Pennsylvania, 19104, United States
Ep0091 802
Philadelphia, Pennsylvania, 19107, United States
Ep0091 838
Cordova, Tennessee, 38018, United States
Ep0091 835
Nashville, Tennessee, 37232, United States
Ep0091 805
Austin, Texas, 78701, United States
Ep0091 844
Austin, Texas, 78758, United States
Ep0091 836
Dallas, Texas, 75231, United States
Ep0091 830
Dallas, Texas, 75390-91, United States
Ep0091 824
Round Rock, Texas, 78681, United States
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San Antonio, Texas, 78229, United States
Ep0091 855
Box Hill, Australia
Ep0091 857
Clayton, Australia
Ep0091 850
Fitzroy, Australia
Ep0091 859
Herston, Australia
Ep0091 852
Melbourne, Australia
Ep0091 853
Melbourne, Australia
Ep0091 856
Randwick, Australia
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Westmead, Australia
Ep0091 102
Bruges, Belgium
Ep0091 101
Brussels, Belgium
Ep0091 105
Ghent, Belgium
Ep0091 100
Leuven, Belgium
Ep0091 150
Blagoevgrad, Bulgaria
Ep0091 151
Pleven, Bulgaria
Ep0091 153
Pleven, Bulgaria
Ep0091 152
Sofia, Bulgaria
Ep0091 154
Sofia, Bulgaria
Ep0091 155
Sofia, Bulgaria
Ep0091 200
Greenfield Park, Canada
Ep0091 205
London, Canada
Ep0091 201
Montreal, Canada
Ep0091 254
Brno, Czechia
Ep0091 255
Ostrava-Poruba, Czechia
Ep0091 250
Prague, Czechia
Ep0091 251
Prague, Czechia
Ep0091 252
Prague, Czechia
Ep0091 253
Prague, Czechia
Ep0091 307
Clermont-Ferrand, France
Ep0091 309
Dijon, France
Ep0091 300
Lille, France
Ep0091 302
Montpellier, France
Ep0091 305
Paris, France
Ep0091 303
Rennes, France
Ep0091 306
Toulouse, France
Ep0091 361
Bad Neustadt an der Saale, Germany
Ep0091 365
Berlin, Germany
Ep0091 362
Bernau, Germany
Ep0091 363
Bielefeld, Germany
Ep0091 358
Bonn, Germany
Ep0091 350
Frankfurt am Main, Germany
Ep0091 360
Freiburg im Breisgau, Germany
Ep0091 364
Hamburg, Germany
Ep0091 368
Jena, Germany
Ep0091 366
Kork, Germany
Ep0091 357
Leipzig, Germany
Ep0091 353
Marburg, Germany
Ep0091 354
München, Germany
Ep0091 351
Münster, Germany
Ep0091 356
Osnabrück, Germany
Ep0091 367
Ravensburg, Germany
Ep0091 301
Strausberg, Germany
Ep0091 352
Tübingen, Germany
Ep0091 400
Budapest, Hungary
Ep0091 403
Budapest, Hungary
Ep0091 402
Debrecen, Hungary
Ep0091 462
Bologna, Italy
Ep0091 450
Cagliari, Italy
Ep0091 461
Foggia, Italy
Ep0091 452
Milan, Italy
Ep0091 459
Pavia, Italy
Ep0091 453
Perugia, Italy
Ep0091 458
Pozzilli, Italy
Ep0091 454
Reggio Calabria, Italy
Ep0091 455
Roma, Italy
Ep0091 457
Roma, Italy
Ep0091 460
Roma, Italy
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Asaka, Japan
Ep0091 511
Fukuoka, Japan
Ep0091 505
Hiroshima, Japan
Ep0091 513
Hōfu, Japan
Ep0091 507
Itami, Japan
Ep0091 503
Kodaira, Japan
Ep0091 514
Kyoto, Japan
Ep0091 512
Nagakute, Japan
Ep0091 510
Niigata, Japan
Ep0091 515
Saitama, Japan
Ep0091 509
Shizuoka, Japan
Ep0091 703
Kaunas, Lithuania
Ep0091 701
Vilnius, Lithuania
Ep0091 702
Vilnius, Lithuania
Ep0091 553
Culiacán, Mexico
Ep0091 552
Mexico City, Mexico
Ep0091 601
Gdansk, Poland
Ep0091 607
Grodzisk Mazowiecki, Poland
Ep0091 605
Katowice, Poland
Ep0091 608
Katowice, Poland
Ep0091 603
Krakow, Poland
Ep0091 604
Lublin, Poland
Ep0091 606
Nowa Sól, Poland
Ep0091 600
Poznan, Poland
Ep0091 609
Poznan, Poland
Ep0091 602
Świdnik, Poland
Ep0091 952
Santa Maria da Feira, Portugal
Ep0091 004
Bardejov, Slovakia
Ep0091 001
Hlohovec, Slovakia
Ep0091 662
Alicante, Spain
Ep0091 651
Barcelona, Spain
Ep0091 652
Barcelona, Spain
Ep0091 658
Barcelona, Spain
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Barcelona, Spain
Ep0091 668
Bilbao, Spain
Ep0091 666
Córdoba, Spain
Ep0091 650
Madrid, Spain
Ep0091 656
Madrid, Spain
Ep0091 660
Madrid, Spain
Ep0091 661
Madrid, Spain
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Málaga, Spain
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Seville, Spain
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Terrassa, Spain
Ep0091 657
Valencia, Spain
Ep0091 667
Valencia, Spain
Ep0091 653
Valladolid, Spain
Ep0091 904
Eskişehir, Turkey (Türkiye)
Ep0091 900
Istanbul, Turkey (Türkiye)
Ep0091 901
Istanbul, Turkey (Türkiye)
Ep0091 752
Birmingham, United Kingdom
Ep0091 751
Cardiff, United Kingdom
Ep0091 756
Inverness, United Kingdom
Ep0091 757
London, United Kingdom
Ep0091 750
Manchester, United Kingdom
Ep0091 753
Swansea, United Kingdom
Related Publications (2)
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: 36176044RESULTKramer 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.
PMID: 37973662RESULT
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 2
- 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
December 7, 2017
First Posted
December 14, 2017
Study Start
February 12, 2018
Primary Completion
January 30, 2020
Study Completion
January 30, 2020
Last Updated
December 19, 2023
Results First Posted
April 9, 2021
Record last verified: 2023-12
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.