Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy (ARISE)

December 15, 2023 updated by: UCB Biopharma S.P.R.L.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

411

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Box Hill, Australia
        • Ep0091 855
      • Clayton, Australia
        • Ep0091 857
      • Fitzroy, Australia
        • Ep0091 850
      • Herston, Australia
        • Ep0091 859
      • Melbourne, Australia
        • Ep0091 852
      • Melbourne, Australia
        • Ep0091 853
      • Randwick, Australia
        • Ep0091 856
      • Westmead, Australia
        • Ep0091 854
  • Belgium
      • Brugge, Belgium
        • Ep0091 102
      • Brussels, Belgium
        • Ep0091 101
      • Gent, Belgium
        • Ep0091 105
      • Leuven, Belgium
        • Ep0091 100
  • Bulgaria
      • Blagoevgrad, Bulgaria
        • Ep0091 150
      • Pleven, Bulgaria
        • Ep0091 151
      • Pleven, Bulgaria
        • Ep0091 153
      • Sofia, Bulgaria
        • Ep0091 152
      • Sofia, Bulgaria
        • Ep0091 154
      • Sofia, Bulgaria
        • Ep0091 155
  • Canada
      • Greenfield Park, Canada
        • Ep0091 200
      • London, Canada
        • Ep0091 205
      • Montréal, Canada
        • Ep0091 201
  • Czechia
      • Brno, Czechia
        • Ep0091 254
      • Ostrava-Poruba, Czechia
        • Ep0091 255
      • Praha, Czechia
        • Ep0091 251
      • Praha 4, Czechia
        • Ep0091 252
      • Praha 5, Czechia
        • Ep0091 250
      • Praha 8, Czechia
        • Ep0091 253
  • France
      • Clermont-Ferrand Cedex 1, France
        • Ep0091 307
      • Dijon, France
        • Ep0091 309
      • Lille, France
        • Ep0091 300
      • Montpellier, France
        • Ep0091 302
      • Paris, France
        • Ep0091 305
      • Rennes, France
        • Ep0091 303
      • Toulouse Cedex 9, France
        • Ep0091 306
  • Germany
      • Bad Neustadt An Der Saale, Germany
        • Ep0091 361
      • Berlin, Germany
        • Ep0091 365
      • Bernau, Germany
        • Ep0091 362
      • Bielefeld, Germany
        • Ep0091 363
      • Bonn, Germany
        • Ep0091 358
      • Frankfurt am main, Germany
        • Ep0091 350
      • Freiburg, Germany
        • Ep0091 360
      • Hamburg, Germany
        • Ep0091 364
      • Jena, Germany
        • Ep0091 368
      • Kork, Germany
        • Ep0091 366
      • Leipzig, Germany
        • Ep0091 357
      • Marburg, Germany
        • Ep0091 353
      • München, Germany
        • Ep0091 354
      • Münster, Germany
        • Ep0091 351
      • Osnabrück, Germany
        • Ep0091 356
      • Ravensburg, Germany
        • Ep0091 367
      • Strausberg, Germany
        • Ep0091 301
      • Tübingen, Germany
        • Ep0091 352
  • Hungary
      • Budapest, Hungary
        • Ep0091 400
      • Budapest, Hungary
        • Ep0091 403
      • Debrecen, Hungary
        • Ep0091 402
  • Italy
      • Bologna, Italy
        • Ep0091 462
      • Cagliari, Italy
        • Ep0091 450
      • Foggia, Italy
        • Ep0091 461
      • Milano, Italy
        • Ep0091 452
      • Pavia, Italy
        • Ep0091 459
      • Perugia, Italy
        • Ep0091 453
      • Pozzilli, Italy
        • Ep0091 458
      • Reggio Calabria, Italy
        • Ep0091 454
      • Roma, Italy
        • Ep0091 455
      • Roma, Italy
        • Ep0091 457
      • Roma, Italy
        • Ep0091 460
  • Japan
      • Asaka, Japan
        • Ep0091 501
      • Fukuoka, Japan
        • Ep0091 511
      • Hiroshima, Japan
        • Ep0091 505
      • Hōfu, Japan
        • Ep0091 513
      • Itami, Japan
        • Ep0091 507
      • Kodaira, Japan
        • Ep0091 503
      • Kyoto, Japan
        • Ep0091 514
      • Nagakute, Japan
        • Ep0091 512
      • Niigata, Japan
        • Ep0091 510
      • Saitama, Japan
        • Ep0091 515
      • Shizuoka, Japan
        • Ep0091 509
  • Lithuania
      • Kaunas, Lithuania
        • Ep0091 703
      • Vilnius, Lithuania
        • Ep0091 701
      • Vilnius, Lithuania
        • Ep0091 702
  • Mexico
      • Culiacán, Mexico
        • Ep0091 553
      • Mexico Distrito Federal, Mexico
        • Ep0091 552
  • Poland
      • Gdańsk, Poland
        • Ep0091 601
      • Grodzisk Mazowiecki, Poland
        • Ep0091 607
      • Katowice, Poland
        • Ep0091 605
      • Katowice, Poland
        • Ep0091 608
      • Kraków, Poland
        • Ep0091 603
      • Lublin, Poland
        • Ep0091 604
      • Nowa Sól, Poland
        • Ep0091 606
      • Poznań, Poland
        • Ep0091 600
      • Poznań, Poland
        • Ep0091 609
      • Świdnik, Poland
        • Ep0091 602
  • Portugal
      • Santa Maria Da Feira, Portugal
        • Ep0091 952
  • Slovakia
      • Bardejov, Slovakia
        • Ep0091 004
      • Hlohovec, Slovakia
        • Ep0091 001
  • Spain
      • Alicante, Spain
        • Ep0091 662
      • Barcelona, Spain
        • Ep0091 651
      • Barcelona, Spain
        • Ep0091 652
      • Barcelona, Spain
        • Ep0091 658
      • Barcelona, Spain
        • Ep0091 664
      • Bilbao, Spain
        • Ep0091 668
      • Córdoba, Spain
        • Ep0091 666
      • Madrid, Spain
        • Ep0091 650
      • Madrid, Spain
        • Ep0091 656
      • Madrid, Spain
        • Ep0091 660
      • Madrid, Spain
        • Ep0091 661
      • Málaga, Spain
        • Ep0091 659
      • Sevilla, Spain
        • Ep0091 663
      • Terrassa, Spain
        • Ep0091 665
      • Valencia, Spain
        • Ep0091 657
      • Valencia, Spain
        • Ep0091 667
      • Valladolid, Spain
        • Ep0091 653
  • Turkey
      • Eskişehir, Turkey
        • Ep0091 904
      • Istanbul, Turkey
        • Ep0091 900
      • Istanbul, Turkey
        • Ep0091 901
  • United Kingdom
      • Birmingham, United Kingdom
        • Ep0091 752
      • Cardiff, United Kingdom
        • Ep0091 751
      • Inverness, United Kingdom
        • Ep0091 756
      • London, United Kingdom
        • Ep0091 757
      • Manchester, United Kingdom
        • Ep0091 750
      • Swansea, United Kingdom
        • Ep0091 753
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85226
        • Ep0091 839
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Ep0091 810
    • California
      • La Jolla, California, United States, 92037
        • Ep0091 815
      • San Francisco, California, United States, 94115
        • Ep0091 801
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • Ep0091 845
    • Florida
      • Ocala, Florida, United States, 34471
        • Ep0091 809
      • Orlando, Florida, United States, 32806
        • Ep0091 823
      • Port Charlotte, Florida, United States, 33952
        • Ep0091 825
      • Tallahassee, Florida, United States, 32308
        • Ep0091 820
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Ep0091 873
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Ep0091 803
    • Illinois
      • Peoria, Illinois, United States, 61637
        • Ep0091 832
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Ep0091 822
      • Bethesda, Maryland, United States, 20817
        • Ep0091 818
    • Minnesota
      • Saint Paul, Minnesota, United States, 55102
        • Ep0091 817
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Ep0091 806
    • New York
      • New York, New York, United States, 10016-48
        • Ep0091 827
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Ep0091 800
      • Philadelphia, Pennsylvania, United States, 19107
        • Ep0091 802
    • Tennessee
      • Cordova, Tennessee, United States, 38018
        • Ep0091 838
      • Nashville, Tennessee, United States, 37232
        • Ep0091 835
    • Texas
      • Austin, Texas, United States, 78701
        • Ep0091 805
      • Austin, Texas, United States, 78758
        • Ep0091 844
      • Dallas, Texas, United States, 75231
        • Ep0091 836
      • Dallas, Texas, United States, 75390-91
        • Ep0091 830
      • Round Rock, Texas, United States, 78681
        • Ep0091 824
      • San Antonio, Texas, United States, 78229
        • Ep0091 870

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Padsevonil dosing regimen 1
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Other: Placebo
Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 2
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Other: Placebo
Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 3
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Other: Placebo
Placebo will be provided matching Padsevonil.
Experimental: Padsevonil dosing regimen 4
Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.
Drug: Padsevonil
Padsevonil in different dosages.
Other: Placebo
Placebo will be provided matching Padsevonil.
Placebo Comparator: Placebo
Subjects randomized to the placebo group will receive a combination of several Placebo tablets to maintain the blinding.
Other: Placebo
Placebo will be provided matching Padsevonil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
Time Frame: 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
Time Frame: 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.
From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
Time Frame: 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.
From Baseline until Safety Follow-Up (up to Week 23)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study
Time Frame: 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 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
75 % Responder Rate Over the 12 Week Maintenance Period
Time Frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
The 75% responder rate, where a responder is a participant experiencing a ≥75% reduction 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
50 % Responder Rate Over the 12 Week Maintenance Period
Time Frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
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.
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
Time Frame: End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
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) was assessed.
End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UCB Biopharma S.P.R.L.

Investigators

  • Study Director: UCB Cares, 001 844 599 2273 (UCB)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 12, 2018

Primary Completion (Actual)

January 30, 2020

Study Completion (Actual)

January 30, 2020

Study Registration Dates

First Submitted

December 7, 2017

First Submitted That Met QC Criteria

December 13, 2017

First Posted (Actual)

December 14, 2017

Study Record Updates

Last Update Posted (Estimated)

December 19, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP0091
  • 2017-003200-48 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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