Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures

NCT ID: NCT02535091

Last Updated: 2024-05-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1345 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-03

Study Completion Date

2022-02-07

Brief Summary

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This is a multicenter, open label study to assess the safety and pharmacokinetics of YKP3089 as adjunctive therapy in subjects with partial onset seizures. Initially, subjects taking phenytoin or phenobarbital will be enrolled followed by additional subjects taking anti-epileptic drugs (AED) other than phenytoin and phenobarbital to further investigate long-term safety.

Detailed Description

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see above

Conditions

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Partial Epilepsy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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YKP3089

Multiple dose

Group Type EXPERIMENTAL

YKP3089

Intervention Type DRUG

see above

Interventions

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YKP3089

see above

Intervention Type DRUG

Other Intervention Names

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other anti-epileptic drug (AED)

Eligibility Criteria

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Inclusion Criteria

1. Male or female and greater than or equal to 18 years of age at the time of signing the informed consent. The upper age limit is 70 years inclusive.
2. Weight at least 30 kg
3. Written informed consent signed by the subject or legal guardian prior to entering the study in accordance with the International Conference on Harmonization Good Clinical Practices (ICH GCP) guidelines. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained. In Germany, only the subject may sign the informed consent form in accordance with ICH guidelines.
4. 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).
5. Have uncontrolled partial seizures and require additional AED therapy despite having been treated with at least one AED within approximately the last 2 years.
6. Currently on stable antiepileptic treatment regimen:

1. Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks prior to Visit 2
2. Vagal nerve stimulator (VNS) will not be counted as an AED; however, the parameters must remain stable for at least 4 weeks prior to baseline. The VNS must have been implanted at least 5 months prior to Visit 1.
3. Benzodiazepines taken at least once per week during the 1 month prior to Visit 1 for epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED and must be continued unchanged throughout the study. Therefore only a maximum of 2 additional approved AEDs will be allowed.
7. Computed tomography (CT) or magnetic resonance imaging (MRI) scan performed within the past 10 years that ruled out a progressive cause of epilepsy. If a CT or MRI has not been performed within the past 10 years, one must be performed prior to randomization.
8. Ability to reach subject by telephone.
9. Use of an acceptable form of birth control by female subjects of childbearing potential

Exclusion Criteria

1. History of any serious drug-induced hypersensitivity reaction (including but not limited to Stevens Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms) or any drug-related rash requiring hospitalization.
2. History of any drug-induced rash or hypersensitivity reaction.
3. History of a first degree relative with a serious cutaneous drug-induced adverse reaction.
4. History of serious systemic disease, including hepatic insufficiency, renal insufficiency, a malignant neoplasm, any disorder in which prognosis for survival is less than 3 months, or any disorder which in the judgment of the investigator will place the subject at excessive risk by participation in a controlled trial
5. Subjects taking phenytoin must not be taking phenobarbital or primidone; subjects taking phenobarbital must not be taking phenytoin or primidone
6. Subjects taking concomitant AEDs other than phenytoin or phenobarbital, must not be taking phenytoin or phenobarbital or primidone
7. Subjects with clinical evidence of phenytoin or phenobarbital toxicity
8. A history of nonepileptic or psychogenic seizures
9. Presence of only nonmotor simple partial seizures or primary generalized epilepsies
10. Presence of Lennox-Gastaut syndrome
11. Scheduled epilepsy surgery within 8 months after Visit 1
12. Subjects implanted with or planning to have implantation of deep brain stimulator
13. Pregnancy or lactation
14. Any clinically significant laboratory abnormality that in the opinion of the investigator would exclude the subject from the study
15. Evidence of significant active hepatic disease. Stable elevations of liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) due to concomitant medication(s) will be allowed if they are less than 3 times the upper limit of normal (ULN)
16. An active central nervous system (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
17. 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
18. Presence of psychotic disorders and/or unstable recurrent affective disorders evident by use of antipsychotics; presence or recent history (within 6 months) of major depressive episode
19. History of alcoholism, drug abuse, or drug addiction within the past 2 years
20. Current use of felbamate with less than 18 months of continuous exposure
21. Current or recent (within the past year) use of vigabatrin or ezogabine. Subjects with a prior history of treatment with vigabatrin must have documentation showing no evidence of a vigabatrin associated clinically significant abnormality in a visual perimetry test. Subjects with a prior history of treatment with ezogabine should have no evidence of retinal abnormalities with funduscopic features similar to those seen in retinal pigment dystrophies.
22. History of status epilepticus within 3 months of Visit 1
23. Screening laboratory investigation demonstrates abnormal renal function
24. Absolute neutrophil count less than 1500/µL
25. Clinical or ECG evidence of serious cardiac disease, including ischemic heart disease, uncontrolled heart failure, and major arrhythmias, or relevant replicated changes in QT intervals (QTcF less than 340 msec or greater than 450 msec in males and greater than 470 msec in females)
26. Platelet counts lower than 80,000/µL in subjects treated with Valproic acid (divalproex sodium) (VPA)
27. A "yes" answer to Question 1 or 2 of the Columbia Suicide Severity Rating Scale (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.
28. More than 1 lifetime suicide attempt
29. Participation in any other trials involving an investigational product or device within 30 days of screening (or longer, as required by local regulations)
30. Current use of any of the following medications: clopidogrel, fluvoxamine, amitriptyline, clomipramine, bupropion, methadone, ifosfamide, cyclophosphamide, efavirenz, fosphenytoin, ethotoin, mephenytoin, or natural progesterone (within 1 month of Visit 1)
31. History of positive antibody/antigen test for hepatitis B, hepatitis C, or HIV
32. Presence of congenital short QT syndrome
33. A history of 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

Principal Investigators

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Marc Kamin, MD

Role: STUDY_DIRECTOR

SK Life Science, Inc.

Locations

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Xen Institute

Phoenix, Arizona, United States

Site Status

Banner-University Medical Center Phoenix

Phoenix, Arizona, United States

Site Status

Arkansas Epilepsy Program

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente - Southern California Medical Group

Anaheim, California, United States

Site Status

Neuro Pain Medical Center

Fresno, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Blue Sky Neurology

Englewood, Colorado, United States

Site Status

Bradenton Research Center Inc

Bradenton, Florida, United States

Site Status

NW FL Neurology Center

Gulf Breeze, Florida, United States

Site Status

Emory Brain Health Center

Atlanta, Georgia, United States

Site Status

Georgia Neurology and Sleep Medicine Associates

Suwanee, Georgia, United States

Site Status

Hawaii Pacific Neuroscience

Honolulu, Hawaii, United States

Site Status

Consultants In Epilepsy and Neurology PLLC

Boise, Idaho, United States

Site Status

MacFarland Clinic

Ames, Iowa, United States

Site Status

Maine Medical Partners Neurology

Scarborough, Maine, United States

Site Status

The John Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Klein, Pavel (Private Practice)

Bethesda, Maryland, United States

Site Status

Neurology Clinic PC

Waldorf, Maryland, United States

Site Status

Minneapolis Clinic of Neurology

Minneapolis, Minnesota, United States

Site Status

Comprehensive Epilepsy Care Center for Children and Adults PC

Chesterfield, Missouri, United States

Site Status

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of Cincinnati, Physicians Company

Cincinnati, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Providence Neurological Specialty Clinic

Portland, Oregon, United States

Site Status

Penn Epilepsy Center, Department of Neurology

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Austin Epilepsy Care Center

Austin, Texas, United States

Site Status

Hunt Regional Medical Partners

Greenville, Texas, United States

Site Status

Baylor Scott and White Research Institute

Temple, Texas, United States

Site Status

University of Virginia, School of Medicine

Charlottesville, Virginia, United States

Site Status

University of Washington School of Medicine

Seattle, Washington, United States

Site Status

UW Medicine, Valley Medical Center

Seattle, Washington, United States

Site Status

Dean and St. Mary's Outpatient Center

Madison, Wisconsin, United States

Site Status

Centro de Educacion Medica e Investigaciones Clinicas (CEMIC)

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Site Status

Hogar de Dia Casa Jesi

Buenos Aires, , Argentina

Site Status

Instituto de Neurociencias de Fundacion Favaloro

Buenos Aires, , Argentina

Site Status

Flinders Medical Centre

Bedford Park, , Australia

Site Status

Eastern Health, Box Hill Hospital

Box Hill, , Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status

Strategic Health Evaluators

Chatswood, , Australia

Site Status

Monash Medical Centre

Clayton, , Australia

Site Status

St. Vincent's Hospital Melbourne

Fitzroy, , Australia

Site Status

Austin Health Melbourne Brain Centre

Heidelberg, , Australia

Site Status

Royal Brisbane & Women's Hospital

Herston, , Australia

Site Status

Alfred Health - The Alfred Hospital

Melbourne, , Australia

Site Status

Melbourne Health (The Royal Melbourne Hospital)

Parkville, , Australia

Site Status

Prince of Wales Hospital

Randwick, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Multiprofile Hospital for Active Treatment Puls AD

Blagoevgrad, , Bulgaria

Site Status

Multiprofile Hospital for Active Treatment of Neurology and Pschiatry "Sv. Naum" EAD

Sofia, , Bulgaria

Site Status

First Multiprofile Hospital for Active Treatment- Sofia EAD

Sofia, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD

Sofia, , Bulgaria

Site Status

Centro Neuropsicologia LTDA.

La Florida, Santiago Metropolitan, Chile

Site Status

Complejo Asistencial Dr. Sotero Del Rio

Puente Alto, Santiago Metropolitan, Chile

Site Status

Hospital Base Valdivia

Valdivia, , Chile

Site Status

Fakultni nemocnice u sv. Anny v Brne

Brno, , Czechia

Site Status

Affidea Praha s.r.o.

Prague, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel

Bielefeld, , Germany

Site Status

University of Bonn, Department of Epileptology

Bonn, , Germany

Site Status

Epilepsiezentrum Kork

Kehl, , Germany

Site Status

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Site Status

Universitätsklinikum Gießen und Marburg GmbH

Marburg, , Germany

Site Status

Universitätsklinikum Münster, Klinik fur Neurologie mit Institut fur Translationale Neurologie-Epileptologie

Münster, , Germany

Site Status

Országos Klinikai Idegtudományi Intézet

Budapest, , Hungary

Site Status

Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz

Debrecen, , Hungary

Site Status

Bacs Kiskun Megyei Korhaz

Kecskemét, , Hungary

Site Status

Neurociencias Estudios Clinicos S.C.

Culiacán, , Mexico

Site Status

Grupo Medico Camino S.C.

Mexico City, , Mexico

Site Status

Human Science Research Trials S. de R.L. de C.V.

Mexico City, , Mexico

Site Status

Centro de Investigacion Grupo Vitamagen

Monterrey, , Mexico

Site Status

Clinical Research Institute S.C.

Tlalnepantla, , Mexico

Site Status

Centrum Neurologii Krzysztof Selmaj

Lodz, Lódzkie, Poland

Site Status

Centrum Leczenia Padaczki i Migreny

Krakow, Malopolski, Poland

Site Status

Fundacja Epileptologii Prof Jerzego Majkowskiego

Warsaw, Masovian Voivodeship, Poland

Site Status

Instytut Psychiatrii i Neurologii

Warsaw, Masovian Voivodeship, Poland

Site Status

Novo-Med Zielinski i wsp. Sp.J.

Katowice, Silesian Voivodeship, Poland

Site Status

Copernicus Podmiot Leczniczy Sp. z o.o.

Gdansk, , Poland

Site Status

FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.P. Serbskiy of MoH of RF

Moscow, , Russia

Site Status

SBHI of Perm Region, Perm Territorial Clinical Hospital, Centre for Multiple Sclerosis

Perm, , Russia

Site Status

FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev of MoH of RF

Saint Petersburg, , Russia

Site Status

FSBI of Science, Institute of Human Brain n.a. N.P. Bekhtereva of RAN, Laboratory of Stereotaxic Methods

Saint Petersburg, , Russia

Site Status

SBHI Samara Regional Clinical Hospital n.a. V.D. Seredavin, Neurology and Neurosurgery Departments

Samara, , Russia

Site Status

SBGEI of HPE Smolensk State Medical University of MoH of RF, Chair Neurology and Neurosurgery

Smolensk, , Russia

Site Status

Clinical Center of Serbia

Belgrade, , Serbia

Site Status

Institute of Mental Health

Belgrade, , Serbia

Site Status

Military Medical Academy

Belgrade, , Serbia

Site Status

Clinical Center Kragujevac

Kragujevac, , Serbia

Site Status

Dong-A University Hospital

Busan, , South Korea

Site Status

Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status

Severance Hospital at Yonsei University Health System

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Konkuk University Medical Center

Seoul, , South Korea

Site Status

Hospital Universitario Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Parque Tecnológico de la Salud

Granada, , Spain

Site Status

Hospital Ruber Internacional

Madrid, , Spain

Site Status

Hospital Universitario Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Faculty of Medicine, Chiang Mai University

Chiang Mai, Muang, Thailand

Site Status

King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University

Bangkok, Pathumwan, Thailand

Site Status

Municipal Institution Dnipropetrovsk Regional Clinical Hospital

Dnipro, , Ukraine

Site Status

Communal Non-Commercial Enterprise of Kharkiv Regional Counsil "Regional clinical psychiatric hospital #3"

Kharkiv, , Ukraine

Site Status

Kharkiv Railway Clinical Hospital #1 of the Health Center Branch of JSC Ukrzaliznytsia

Kharkiv, , Ukraine

Site Status

Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital"

Lviv, , Ukraine

Site Status

Municipal Non-Commercial Enterprise Odesa Regional Medical Center for Mental Health of Odessa Regional Council

Odesa, , Ukraine

Site Status

Municipal Non-Commercial Enterprise Odesa Regional Medical Center

Odesa, , Ukraine

Site Status

Municipal Institution Odesa Regional Psychiatric Hospital #2

Oleksandrivka, , Ukraine

Site Status

Municipal Non-Commercial Enterprise "Ternopil Regional Clinical Psychoneurological Hospital" of Ternopil Regional Council

Ternopil, , Ukraine

Site Status

Communal Non-profit Enterprise "Vinnytsia Regional Clinical Psycho-Neurological Hospital"

Vinnytsia, , Ukraine

Site Status

Countries

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United States Argentina Australia Bulgaria Chile Czechia Germany Hungary Mexico Poland Russia Serbia South Korea Spain Sweden Thailand Ukraine

References

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O'Dwyer R, Stern S, Wade CT, Guggilam A, Rosenfeld WE. Safety and Efficacy of Cenobamate for the Treatment of Focal Seizures in Older Patients: Post Hoc Analysis of a Phase III, Multicenter, Open-Label Study. Drugs Aging. 2024 Mar;41(3):251-260. doi: 10.1007/s40266-024-01102-3. Epub 2024 Mar 6.

Reference Type DERIVED
PMID: 38446341 (View on PubMed)

Sperling MR, Abou-Khalil B, Aboumatar S, Bhatia P, Biton V, Klein P, Krauss GL, Vossler DG, Wechsler R, Ferrari L, Grall M, Rosenfeld WE. Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study. Epilepsia. 2021 Dec;62(12):3005-3015. doi: 10.1111/epi.17091. Epub 2021 Oct 11.

Reference Type DERIVED
PMID: 34633084 (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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YKP3089C021

Identifier Type: -

Identifier Source: org_study_id

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