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

Drug-Resistant Epilepsy Clinical Trial

— DUET  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03739840
• Other study ID #: EP0092
• Secondary ID: 2018-002303-33
• Status: Terminated
• Phase: Phase 3
• Start date: March 6, 2019
• Est. completion date: September 28, 2020

Study information

• Verified date: December 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 232
• Est. completion date: September 28, 2020
• Est. primary completion date: September 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Drug-Resistant Epilepsy
• Epilepsy
• Focal-Onset Seizures
• Seizures

Intervention

Drug:
• Padsevonil
Padsevonil in different dosages.
• Placebo
Placebo will be provided matching padsevonil.

Locations

Country	Name	City	State
Australia	Ep0092 855	Box Hill
Australia	Ep0092 861	Camperdown
Australia	Ep0092 850	Fitzroy
Australia	Ep0092 853	Heidelberg
Australia	Ep0092 852	Melbourne
Belgium	Ep0092 109	Brussels
Belgium	Ep0092 107	Ottignies
Bosnia and Herzegovina	Ep0092 080	Bihac
Bosnia and Herzegovina	Ep0092 077	Mostar
Bosnia and Herzegovina	Ep0092 075	Sarajevo
Bosnia and Herzegovina	Ep0092 082	Tuzla
Bulgaria	Ep0092 150	Blagoevgrad
Bulgaria	Ep0092 151	Pleven
Bulgaria	Ep0092 156	Pleven
Bulgaria	Ep0092 154	Sofia
Croatia	Ep0092 125	Zagreb
Croatia	Ep0092 126	Zagreb
Croatia	Ep0092 127	Zagreb
Croatia	Ep0092 128	Zagreb
Czechia	Ep0092 254	Brno
Czechia	Ep0092 258	Ostrava
Czechia	Ep0092 250	Praha 5
Czechia	Ep0092 251	Praha 6
Denmark	Ep0092 016	Aarhus
Denmark	Ep0092 015	Odense
Estonia	Ep0092 276	Tallinn
Estonia	Ep0092 277	Tallinn
Estonia	Ep0092 275	Tartu
Finland	Ep0092 027	Tampere
France	Ep0092 312	Lyon
France	Ep0092 310	Paris
France	Ep0092 301	Strasbourg
Germany	Ep0092 365	Berlin
Germany	Ep0092 362	Bernau
Germany	Ep0092 363	Bielefeld
Germany	Ep0092 350	Frankfurt
Germany	Ep0092 368	Jena
Germany	Ep0092 357	Leipzig
Germany	Ep0092 376	Regensburg
Greece	Ep0092 425	Ioánnina
Greece	Ep0092 426	Thessaloníki
Greece	Ep0092 427	Thessaloníki
Greece	Ep0092 428	Thessaloníki
Hungary	Ep0092 403	Budapest
Hungary	Ep0092 405	Debrecen
Hungary	Ep0092 404	Pécs
Ireland	Ep0092 035	Cork
Ireland	Ep0092 036	Dublin
Italy	Ep0092 452	Milano
Japan	Ep0092 526	Asahikawa
Japan	Ep0092 501	Asaka
Japan	Ep0092 521	Bunkyo-Ku
Japan	Ep0092 525	Bunkyo-Ku
Japan	Ep0092 504	Hamamatsu
Japan	Ep0092 505	Hiroshima
Japan	Ep0092 513	Hofu
Japan	Ep0092 507	Itami
Japan	Ep0092 531	Izumi
Japan	Ep0092 539	Kumamoto
Japan	Ep0092 533	Kure
Japan	Ep0092 514	Kyoto
Japan	Ep0092 512	Nagakute
Japan	Ep0092 522	Omura
Japan	Ep0092 530	Osaka-sayama
Japan	Ep0092 515	Saitama
Japan	Ep0092 508	Sapporo
Japan	Ep0092 527	Shinagawa-Ku
Japan	Ep0092 509	Shizuoka
Japan	Ep0092 529	Yonago
Norway	Ep0092 775	Sandvika
Poland	Ep0092 605	Katowice
Poland	Ep0092 616	Katowice
Poland	Ep0092 603	Kraków
Poland	Ep0092 614	Kraków
Poland	Ep0092 612	Lódz
Poland	Ep0092 610	Lublin
Poland	Ep0092 620	Lublin
Poland	Ep0092 606	Nowa Sól
Poland	Ep0092 611	Warszawa
Poland	Ep0092 615	Wroclaw
Poland	Ep0092 619	Zamosc
Poland	Ep0092 618	Zgierz
Portugal	Ep0092 952	Aveiro
Portugal	Ep0092 950	Matosinhos
Romania	Ep0092 925	Bucuresti
Romania	Ep0092 926	Bucuresti
Romania	Ep0092 927	Târgu-Mures
Serbia	Ep0092 327	Belgrade
Serbia	Ep0092 325	Novi Sad
Slovakia	Ep0092 004	Bardejov
Spain	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 676	Zaragoza
Sweden	Ep0092 576	Göteborg
Sweden	Ep0092 575	Linköping
Switzerland	Ep0092 053	Zürich
Turkey	Ep0092 913	Ankara
Turkey	Ep0092 915	Antalya
Turkey	Ep0092 900	Istanbul
Turkey	Ep0092 906	Istanbul
Turkey	Ep0092 909	Istanbul
Turkey	Ep0092 908	Trabzon
United Kingdom	Ep0092 766	Brighton
United Kingdom	Ep0092 750	Manchester
United Kingdom	Ep0092 764	Swansea
United States	Ep0092 630	Ames	Iowa
United States	Ep0092 880	Anderson	Indiana
United States	Ep0092 822	Baltimore	Maryland
United States	Ep0092 818	Bethesda	Maryland
United States	Ep0092 889	Boston	Massachusetts
United States	Ep0092 892	Bradenton	Florida
United States	Ep0092 895	Bronx	New York
United States	Ep0092 878	Brooklyn	New York
United States	Ep0092 633	Carlsbad	California
United States	Ep0092 839	Chandler	Arizona
United States	Ep0092 890	Chapel Hill	North Carolina
United States	Ep0092 884	Charlotte	North Carolina
United States	Ep0092 829	Charlottesville	Virginia
United States	Ep0092 642	Columbus	Ohio
United States	Ep0092 638	Fort Wayne	Indiana
United States	Ep0092 645	Golden Valley	Minnesota
United States	Ep0092 640	Hialeah	Florida
United States	Ep0092 803	Honolulu	Hawaii
United States	Ep0092 641	Jacksonville	Florida
United States	Ep0092 707	Lexington	Kentucky
United States	Ep0092 644	Minneapolis	Minnesota
United States	Ep0092 876	New York	New York
United States	Ep0092 647	Oklahoma City	Oklahoma
United States	Ep0092 629	Orange	California
United States	Ep0092 823	Orlando	Florida
United States	Ep0092 802	Philadelphia	Pennsylvania
United States	Ep0092 882	Portland	Oregon
United States	Ep0092 639	Renton	Washington
United States	Ep0092 893	Syracuse	New York
United States	Ep0092 881	Tucson	Arizona
United States	Ep0092 637	Urbana	Illinois
United States	Ep0092 845	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Croatia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Japan,  Norway,  Poland,  Portugal,  Romania,  Serbia,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (1)

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-bli — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Baseline over the 12 Week Maintenance Period (up to Week 16)
Primary	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.	From Baseline until Safety Follow-Up (up to Week 23)
Primary	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.	From Baseline until Safety Follow-Up (up to Week 23)
Primary	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.	From Baseline until Safety Follow-Up (up to Week 23)
Secondary	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.	From Baseline over the 12 Week Maintenance Period (up to Week 16)
Secondary	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.	From Baseline over the 12 Week Maintenance Period (up to Week 16)
Secondary	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.	From Baseline over the 12 Week Maintenance Period (up to Week 16)