A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures

NCT ID: NCT01866111

Last Updated: 2025-06-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

437 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2021-10-31

Brief Summary

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This is a multicenter, double-blind, randomized, placebo-controlled dose response study, with an 8-week prospective baseline and an 18 week double-blind treatment period (including a 6-week titration phase and 12 week maintenance phase), followed by a 3-week blinded study drug taper period (for subjects leaving the study) or a 2-week blinded conversion period (for subjects who will participate in the open-label extension).

The primary objective of this study is to determine the effective dose range of YKP3089 as adjunctive therapy for the treatment of partial seizures.

The trial will also evaluate the safety and tolerability of YKP3089 in the partial epilepsy population.

Detailed Description

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Conditions

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Partial Epilepsy

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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Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

YKP3089 Low Dose

YKP3089 Low Dose

Group Type EXPERIMENTAL

YKP3089

Intervention Type DRUG

YKP3089 Medium Dose

YKP3089 Medium Dose

Group Type EXPERIMENTAL

YKP3089

Intervention Type DRUG

YKP3089 High Dose

YKP3089 High Dose

Group Type EXPERIMENTAL

YKP3089

Intervention Type DRUG

Interventions

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YKP3089

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Weight at least 40 kg
* A diagnosis of partial epilepsy according to the International League Against Epilepsy's Classification of Epileptic Seizures. Diagnosis should have been established by clinical history and an electroencephalogram (EEG) that is consistent with localization related epilepsy; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history)
* Have uncontrolled partial seizures despite having been treated with at least 1 AED within approximately the last 2 years
* During the 8-week baseline period, subjects must have at least 8 partial seizures including only simple partial seizures with motor component, complex partial seizures, or secondarily generalized seizures without a seizure-free interval of greater than 25 days any time during the 8 weeks baseline. Subjects must have at least 3 of these partial seizures during each of the two consecutive 4-week segments of the baseline period
* Currently on stable antiepileptic treatment regimen.

Exclusion Criteria

* A history of nonepileptic or psychogenic seizures
* Presence of only nonmotor simple partial seizures or primary generalized epilepsies
* Presence or previous history of Lennox-Gastaut syndrome
* An active CNS infection, demyelinating disease, degenerative neurologic disease, or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results
* Any clinically significant psychiatric illness, psychological, or behavioral problems that, in the opinion of the Investigator, would interfere with the subject's ability to participate in the study
* History of alcoholism, drug abuse, or drug addiction within the past 2 years
* History of status epilepticus within 3 months of Visit 1
* A "yes" answer to Question 1 or 2 of the C-SSRS (Baseline/Screening version) Ideation Section in the past 6 months or a "yes" answer to any of the Suicidal Behavior Questions in the past 2 years
* More than 1 lifetime suicide attempt
* Participation in any other trials involving an investigational product or device within 30 days of screening (or longer, as required by local regulations)
* A history of any previous exposure to YKP3089
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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SK Life Science, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics

Phoenix, Arizona, United States

Site Status

Clinical Trials, Inc.

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente, Department of Neurology

Anaheim, California, United States

Site Status

Neuro-Pain Medical Center

Fresno, California, United States

Site Status

West Los Angeles VA Medical Center, Clinical Research Center

Los Angeles, California, United States

Site Status

Neuroresearch, Inc. - Torrance

Torrance, California, United States

Site Status

Neuroresearch II, Inc.

Ventura, California, United States

Site Status

Bradenton Research Center, Inc.

Bradenton, Florida, United States

Site Status

Lovelace Scientific Resources, Inc.

Sarasota, Florida, United States

Site Status

Consultants in Epilepsy & Neurology, PLLC

Boise, Idaho, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Site Status

Neurology Clinic PC

Waldorf, Maryland, United States

Site Status

The Comprehensive Epilepsy Care Center for Children and Adults

St Louis, Missouri, United States

Site Status

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Site Status

NYU Comprehensive Epilepsy Center

New York, New York, United States

Site Status

The Neurological Institute, PA

Charlotte, North Carolina, United States

Site Status

Thomas Jefferson Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Epilepsy Clinic

Nashville, Tennessee, United States

Site Status

Austin Epilepsy Care Center

Austin, Texas, United States

Site Status

University of Virginia Comprehensive Epilepsy Program

Charlottesville, Virginia, United States

Site Status

Institute of Neurological Sciences, Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

St. Vincent's Hospital (Melbourne)

Fitzroy, Victoria, Australia

Site Status

Epilepsy Research Centre, Melbourne Brain Centre

Heidelberg, Victoria, Australia

Site Status

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status

University Multiprofile Hpspital for Active Treatment "Sveti Georgi" EAD, Clinic of Neurological Diseases

Plovdiv, , Bulgaria

Site Status

"First Multiprofile Hospital for Active Treatment - Sofia" EAD, Neurology Clinic

Sofia, , Bulgaria

Site Status

University of Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD, Clinic of Neurological Diseases

Sofia, , Bulgaria

Site Status

Fakultní nemocnice Ostrava, Neurologická klinika

Ostrava, , Czechia

Site Status

Mediscan Group, s.r.o

Prague, , Czechia

Site Status

Fakultni nemocnice v Motole, Neurologická klinika

Prague, , Czechia

Site Status

CHU - Service Neurophysiologie Clinique

Dijon, , France

Site Status

Hôpital Central - CHU de Nancy - Service de Neurologie

Nancy, , France

Site Status

Epilepsiezentrum Berlin- Bradenburg, Epilepsieklinik "Tabor"

Bernau bei Berlin, , Germany

Site Status

Krankenhaus Mara gGmbH, Epilepsiezentrum Bethel

Bielefeld, , Germany

Site Status

Epilepsiezentrum Kork

Kehl, , Germany

Site Status

Országos Klinikai Idegtudományi Intézet

Budapest, , Hungary

Site Status

Department of Neurology, Hadassah University Hospital Ein Kerem, Kiryat Hadassah

Jerusalem, , Israel

Site Status

Western Galilee Hospital, Department of Neurology

Nahariya, , Israel

Site Status

The Chaim Sheba Medical Center, Department of Neurology

Ramat Gan, , Israel

Site Status

M.A. - LEK A.M. Maciejowscy S.C. Centrum Terapii SM

Katowice, , Poland

Site Status

NOVO-MED Zielinski I Wspolnicy Spolka Jawna

Katowice, , Poland

Site Status

NZOZ Centrum Medyczne "Dendryt"

Katowice, , Poland

Site Status

Fundacja Epileptologii profesora Jerzego Majkowskiego

Warsaw, , Poland

Site Status

Instytut Psychaitrii I Neurologii, II Klinika Neurologiczna

Warsaw, , Poland

Site Status

Roceanu Adina Maria Neurology Individual Medical Center

Bucharest, , Romania

Site Status

Sapiens Medical Center SRL

Bucharest, , Romania

Site Status

Clinical of Neurology, Clinical Center of Serbia

Belgrade, , Serbia

Site Status

Institute of Mental Health

Belgrade, , Serbia

Site Status

Clinical Hospital Center Kragujevac

Kragujevac, , Serbia

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Konkuk University Medical Center

Seoul, , South Korea

Site Status

Hospital Universitario San Cecilio - Servicio de Neurologia

Granada, , Spain

Site Status

Hospital Ruber Internacional - Programa Epilepsia

Madrid, , Spain

Site Status

Fundación Jiminez Diaz-Servicio de Neurologia

Madrid, , Spain

Site Status

Hospital Clinico Universitario San Carlos, Serv. Neurologia

Madrid, , Spain

Site Status

Hospital Universitario y Politecnico La Fe - Servicio Neurologia

Valencia, , Spain

Site Status

Srinagarind Hospital

Na Muang, Changwat Khon Kaen, Thailand

Site Status

Neurology of Kharkiv Medical Academy of Postgraduate Education based on Department of Neurology #3 of State Treatment and Prevention Institution "Central Clinical Hospital of Ukrzaliznytsya"

Kharkiv, , Ukraine

Site Status

TDC "Epilepsy" based on Department #19 of Kiev Territorial Medical Association "Psychiatry"

Kyiv, , Ukraine

Site Status

Lviv Regional Antiepileptic Center based on Department of Neurology of Lviv Regional Clinical Hospital and Chair of Neurology of Lviv National Medical University n.a. Danylo Galytskyy

Lviv, , Ukraine

Site Status

MI "Odessa Regional Clinical Hospital," Neurological and Neurosurgical Center based on Neurosurgery Department

Odesa, , Ukraine

Site Status

Department #2 of Regional Clinical Center of Neurosurgery and Neurology

Uzhhorod, , Ukraine

Site Status

Countries

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United States Australia Bulgaria Czechia France Germany Hungary Israel Poland Romania Serbia South Korea Spain Thailand Ukraine

References

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Klein P, Aboumatar S, Brandt C, Dong F, Krauss GL, Mizne S, Sanchez-Alvarez JC, Steinhoff BJ, Villanueva V. Long-term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures. Neurology. 2022 Sep 5;99(10):e989-e998. doi: 10.1212/WNL.0000000000200792.

Reference Type DERIVED
PMID: 35705501 (View on PubMed)

Rosenfeld WE, Nisman A, Ferrari L. Efficacy of adjunctive cenobamate based on number of concomitant antiseizure medications, seizure frequency, and epilepsy duration at baseline: A post-hoc analysis of a randomized clinical study. Epilepsy Res. 2021 May;172:106592. doi: 10.1016/j.eplepsyres.2021.106592. Epub 2021 Feb 18.

Reference Type DERIVED
PMID: 33662894 (View on PubMed)

Krauss GL, Klein P, Brandt C, Lee SK, Milanov I, Milovanovic M, Steinhoff BJ, Kamin M. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020 Jan;19(1):38-48. doi: 10.1016/S1474-4422(19)30399-0. Epub 2019 Nov 14.

Reference Type DERIVED
PMID: 31734103 (View on PubMed)

Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII). Epilepsy Res. 2015 Mar;111:85-141. doi: 10.1016/j.eplepsyres.2015.01.001. Epub 2015 Jan 19.

Reference Type DERIVED
PMID: 25769377 (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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YKP3089C017

Identifier Type: -

Identifier Source: org_study_id

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