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

NCT ID: NCT03373383

Last Updated: 2023-12-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

411 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-12

Study Completion Date

2020-01-30

Brief Summary

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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.

Detailed Description

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Conditions

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Drug-resistant Epilepsy Focal-Onset Seizures

Keywords

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Epilepsy Padsevonil

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Padsevonil dosing regimen 1

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Group Type EXPERIMENTAL

Padsevonil

Intervention Type DRUG

Padsevonil in different dosages.

Placebo

Intervention Type OTHER

Placebo will be provided matching Padsevonil.

Padsevonil dosing regimen 2

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Group Type EXPERIMENTAL

Padsevonil

Intervention Type DRUG

Padsevonil in different dosages.

Placebo

Intervention Type OTHER

Placebo will be provided matching Padsevonil.

Padsevonil dosing regimen 3

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Group Type EXPERIMENTAL

Padsevonil

Intervention Type DRUG

Padsevonil in different dosages.

Placebo

Intervention Type OTHER

Placebo will be provided matching Padsevonil.

Padsevonil dosing regimen 4

Subjects will be randomized to receive a combination of tablets of Padsevonil and Placebo (as appropriate) to maintain the blinding.

Group Type EXPERIMENTAL

Padsevonil

Intervention Type DRUG

Padsevonil in different dosages.

Placebo

Intervention Type OTHER

Placebo will be provided matching Padsevonil.

Placebo

Subjects randomized to the placebo group will receive a combination of several Placebo tablets to maintain the blinding.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo will be provided matching Padsevonil.

Interventions

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Padsevonil

Padsevonil in different dosages.

Intervention Type DRUG

Placebo

Placebo will be provided matching Padsevonil.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UCB Biopharma S.P.R.L.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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UCB Cares

Role: STUDY_DIRECTOR

001 844 599 2273 (UCB)

Locations

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Chandler, Arizona, United States

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Little Rock, Arkansas, United States

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La Jolla, California, United States

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San Francisco, California, United States

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Washington D.C., District of Columbia, United States

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Ocala, Florida, United States

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Orlando, Florida, United States

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Port Charlotte, Florida, United States

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Tallahassee, Florida, United States

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Atlanta, Georgia, United States

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Honolulu, Hawaii, United States

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Peoria, Illinois, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Saint Paul, Minnesota, United States

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Hackensack, New Jersey, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Cordova, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Round Rock, Texas, United States

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San Antonio, Texas, United States

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Box Hill, , Australia

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Clayton, , Australia

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Fitzroy, , Australia

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Herston, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Randwick, , Australia

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Westmead, , Australia

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Bruges, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Blagoevgrad, , Bulgaria

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Pleven, , Bulgaria

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Pleven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Greenfield Park, , Canada

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London, , Canada

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Montreal, , Canada

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Brno, , Czechia

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Ostrava-Poruba, , Czechia

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Prague, , Czechia

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Clermont-Ferrand, , France

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Lille, , France

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Paris, , France

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Rennes, , France

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Toulouse, , France

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Bad Neustadt an der Saale, , Germany

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Berlin, , Germany

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Bernau, , Germany

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Bielefeld, , Germany

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Bonn, , Germany

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Jena, , Germany

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Kork, , Germany

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Leipzig, , Germany

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Marburg, , Germany

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München, , Germany

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Münster, , Germany

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Osnabrück, , Germany

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Itami, , Japan

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Niigata, , Japan

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Shizuoka, , Japan

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Kaunas, , Lithuania

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Culiacán, , Mexico

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Mexico City, , Mexico

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Gdansk, , Poland

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Grodzisk Mazowiecki, , Poland

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Lublin, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Świdnik, , Poland

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Santa Maria da Feira, , Portugal

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Hlohovec, , Slovakia

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Alicante, , Spain

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Málaga, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valladolid, , Spain

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Eskişehir, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Cardiff, , United Kingdom

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Inverness, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Swansea, , United Kingdom

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Countries

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United States Australia Belgium Bulgaria Canada Czechia France Germany Hungary Italy Japan Lithuania Mexico Poland Portugal Slovakia Spain Turkey (Türkiye) United Kingdom

References

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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.

Reference Type RESULT
PMID: 36176044 (View on PubMed)

Kramer 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.

Reference Type RESULT
PMID: 37973662 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-003200-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EP0091

Identifier Type: -

Identifier Source: org_study_id