AzTrials
AzTrials

Drug-Resistant EpilepsyPhase 3DUETNCT03739840

A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy

A Phase 3 study testing Padsevonil in people with Drug-Resistant Epilepsy and Focal-Onset Seizures, run by UCB Biopharma SRL at 141 sites in 28 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Drug-Resistant Epilepsy, Focal-Onset Seizures
What is being tested?
Padsevonil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
232 participants
Where
141 sitesin 28 countries
Study dates
6 Mar 2019to 28 Sep 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

141 sites in 28 countries.

141 sites in 28 countries

United States32 sites
  • Ep0092 630

    Ames, Iowa, 50010

  • Ep0092 880

    Anderson, Indiana, 46011

  • Ep0092 822

    Baltimore, Maryland, 21287

  • Ep0092 818

    Bethesda, Maryland, 20817

  • Ep0092 889

    Boston, Massachusetts, 02215

  • Ep0092 892

    Bradenton, Florida, 34209

  • Ep0092 878

    Brooklyn, New York, 11203

  • Ep0092 633

    Carlsbad, California, 92011

  • Ep0092 839

    Chandler, Arizona, 85226

  • Ep0092 890

    Chapel Hill, North Carolina, 27599

  • Ep0092 884

    Charlotte, North Carolina, 28204

  • Ep0092 829

    Charlottesville, Virginia, 22903

  • Ep0092 642

    Columbus, Ohio, 43210

  • Ep0092 638

    Fort Wayne, Indiana, 46804

  • Ep0092 645

    Golden Valley, Minnesota, 55422

  • Ep0092 640

    Hialeah, Florida, 33016

  • Ep0092 803

    Honolulu, Hawaii, 96817

  • Ep0092 641

    Jacksonville, Florida, 32209

  • Ep0092 707

    Lexington, Kentucky, 40536

  • Ep0092 644

    Minneapolis, Minnesota, 55416

  • Ep0092 876

    New York, New York, 10075

  • Ep0092 647

    Oklahoma City, Oklahoma, 73106

  • Ep0092 629

    Orange, California, 92868

  • Ep0092 823

    Orlando, Florida, 32806

  • Ep0092 802

    Philadelphia, Pennsylvania, 19107

  • Ep0092 882

    Portland, Oregon, 97225

  • Ep0092 639

    Renton, Washington, 98055

  • Ep0092 893

    Syracuse, New York, 13210

  • Ep0092 895

    The Bronx, New York, 10467

  • Ep0092 881

    Tucson, Arizona, 85724

  • Ep0092 637

    Urbana, Illinois, 61801

  • Ep0092 845

    Washington D.C., District of Columbia, 20037

Other trials in United States

Japan20 sites
  • Ep0092 526

    Asahikawa

  • Ep0092 501

    Asaka

  • Ep0092 521

    Bunkyō City

  • Ep0092 525

    Bunkyō City

  • Ep0092 504

    Hamamatsu

  • Ep0092 505

    Hiroshima

  • Ep0092 513

    Hōfu

  • Ep0092 507

    Itami

  • Ep0092 531

    Izumi

  • Ep0092 539

    Kumamoto

  • Ep0092 533

    Kure

  • Ep0092 514

    Kyoto

  • Ep0092 512

    Nagakute

  • Ep0092 522

    Ōmura

  • Ep0092 530

    Ōsaka-sayama

  • Ep0092 515

    Saitama

  • Ep0092 508

    Sapporo

  • Ep0092 527

    Shinagawa-Ku

  • Ep0092 509

    Shizuoka

  • Ep0092 529

    Yonago

Other trials in Japan

Poland12 sites
  • Ep0092 605

    Katowice

  • Ep0092 616

    Katowice

  • Ep0092 603

    Krakow

  • Ep0092 614

    Krakow

  • Ep0092 612

    Lodz

  • Ep0092 610

    Lublin

  • Ep0092 620

    Lublin

  • Ep0092 606

    Nowa Sól

  • Ep0092 611

    Warsaw

  • Ep0092 615

    Wroclaw

  • Ep0092 619

    Zamość

  • Ep0092 618

    Zgierz

Other trials in Poland

Germany7 sites
  • Ep0092 365

    Berlin

  • Ep0092 362

    Bernau

  • Ep0092 363

    Bielefeld

  • Ep0092 350

    Frankfurt

  • Ep0092 368

    Jena

  • Ep0092 357

    Leipzig

  • Ep0092 376

    Regensburg

Other trials in Germany

Spain7 sites
  • Ep0092 662

    Alicante

  • Ep0092 651

    Barcelona

  • Ep0092 652

    Barcelona

  • Ep0092 658

    Barcelona

  • Ep0092 674

    Madrid

  • Ep0092 657

    Valencia

  • Ep0092 676

    Zaragoza

Other trials in Spain

Turkey (Türkiye)6 sites
  • Ep0092 913

    Ankara

  • Ep0092 915

    Antalya

  • Ep0092 900

    Istanbul

  • Ep0092 906

    Istanbul

  • Ep0092 909

    Istanbul

  • Ep0092 908

    Trabzon

Other trials in Turkey (Türkiye)

Australia5 sites
  • Ep0092 855

    Box Hill

  • Ep0092 861

    Camperdown

  • Ep0092 850

    Fitzroy

  • Ep0092 853

    Heidelberg

  • Ep0092 852

    Melbourne

Other trials in Australia

Bosnia and Herzegovina4 sites
  • Ep0092 080

    Bihać

  • Ep0092 077

    Mostar

  • Ep0092 075

    Sarajevo

  • Ep0092 082

    Tuzla

Other trials in Bosnia and Herzegovina

Bulgaria4 sites
  • Ep0092 150

    Blagoevgrad

  • Ep0092 151

    Pleven

  • Ep0092 156

    Pleven

  • Ep0092 154

    Sofia

Other trials in Bulgaria

Croatia4 sites
  • Ep0092 125

    Zagreb

  • Ep0092 126

    Zagreb

  • Ep0092 127

    Zagreb

  • Ep0092 128

    Zagreb

Other trials in Croatia

Czechia4 sites
  • Ep0092 254

    Brno

  • Ep0092 258

    Ostrava

  • Ep0092 250

    Prague

  • Ep0092 251

    Prague

Other trials in Czechia

Greece4 sites
  • Ep0092 425

    Ioannina

  • Ep0092 426

    Thessaloniki

  • Ep0092 427

    Thessaloniki

  • Ep0092 428

    Thessaloniki

Other trials in Greece

Estonia3 sites
  • Ep0092 276

    Tallinn

  • Ep0092 277

    Tallinn

  • Ep0092 275

    Tartu

Other trials in Estonia

France3 sites
  • Ep0092 312

    Lyon

  • Ep0092 310

    Paris

  • Ep0092 301

    Strasbourg

Other trials in France

Hungary3 sites
  • Ep0092 403

    Budapest

  • Ep0092 405

    Debrecen

  • Ep0092 404

    Pécs

Other trials in Hungary

Romania3 sites
  • Ep0092 925

    Bucharest

  • Ep0092 926

    Bucharest

  • Ep0092 927

    Târgu Mureş

Other trials in Romania

United Kingdom3 sites
  • Ep0092 766

    Brighton

  • Ep0092 750

    Manchester

  • Ep0092 764

    Swansea

Other trials in United Kingdom

Belgium2 sites
  • Ep0092 109

    Brussels

  • Ep0092 107

    Ottignies

Other trials in Belgium

Denmark2 sites
  • Ep0092 016

    Aarhus

  • Ep0092 015

    Odense

Other trials in Denmark

Ireland2 sites
  • Ep0092 035

    Cork

  • Ep0092 036

    Dublin

Other trials in Ireland

Portugal2 sites
  • Ep0092 952

    Aveiro

  • Ep0092 950

    Matosinhos Municipality

Other trials in Portugal

Serbia2 sites
  • Ep0092 327

    Belgrade

  • Ep0092 325

    Novi Sad

Other trials in Serbia

Sweden2 sites
  • Ep0092 576

    Gothenburg

  • Ep0092 575

    Linköping

Other trials in Sweden

Finland1 site
  • Ep0092 027

    Tampere

Other trials in Finland

Italy1 site
  • Ep0092 452

    Milan

Other trials in Italy

Norway1 site
  • Ep0092 775

    Sandvika

Other trials in Norway

Slovakia1 site
  • Ep0092 004

    Bardejov

Other trials in Slovakia

Switzerland1 site
  • Ep0092 053

    Zurich

Other trials in Switzerland

About this study

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

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.

Being tested
Padsevonil, Placebo
Keywords
Epilepsy, Padsevonil
Medical subject headings
Drug Resistant Epilepsy, Seizures, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PadsevonilDrug

    Padsevonil in different dosages.

  • PlaceboDrug

    Placebo will be provided matching padsevonil.

Study groups in NCT03739840
Study groupRoleWhat they receive
Padsevonil dosing regimen 1ExperimentalSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Receives: Drug: Padsevonil; Drug: Placebo
Padsevonil dosing regimen 2ExperimentalSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Receives: Drug: Padsevonil; Drug: Placebo
Padsevonil dosing regimen 3ExperimentalSubjects will be randomized to receive a combination of tablets of padsevonil and placebo (as appropriate) to maintain the blinding.
Receives: Drug: Padsevonil; Drug: Placebo
PlaceboPlacebo comparatorSubjects randomized to the placebo group will receive a combination of several placebo tablets to maintain the blinding.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 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.

    Measured: From Baseline over the 12 Week Maintenance Period (up to Week 16)

  2. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

    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.

    Measured: From Baseline until Safety Follow-Up (up to Week 23)

  3. 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. 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.

    Measured: From Baseline until Safety Follow-Up (up to Week 23)

  4. Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

    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.

    Measured: From Baseline until Safety Follow-Up (up to Week 23)

Secondary outcomes (3)
  1. 75% Responder Rate From Baseline Over the 12-week Maintenance Period

    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.

    Measured: From Baseline over the 12 Week Maintenance Period (up to Week 16)

  2. 50% Responder Rate From Baseline Over the 12-week Maintenance Period

    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.

    Measured: From Baseline over the 12 Week Maintenance Period (up to Week 16)

  3. Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12-week Maintenance Period

    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.

    Measured: From Baseline over the 12 Week Maintenance Period (up to Week 16)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2018
  2. Study start6 Mar 2019
  3. Primary completion28 Sep 2020
  4. Study completion28 Sep 2020

Why it stopped: Based on available data, UCB has decided to stop development of padsevonil as adjunctive treatment of focal-onset seizure

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
232 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03739840
Sponsor's protocol ID
EP0092
Other IDs
2018-002303-33, 2018
Acronym
DUET
Status last verified
Dec 2022
First submitted
9 Nov 2018
Last updated
21 Dec 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 36176044

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Padsevonil in people with Drug-Resistant Epilepsy and Focal-Onset Seizures, run by UCB Biopharma SRL at 141 sites in 28 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 141 sites in United States, Japan, Poland, Germany, Spain and 23 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (up to Week 16)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03739840, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2022.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in