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

NCT02535091 | Completed Phase 3 Results

• 1 other identifier: YKP3089C021
• Study Type: interventional
• Target: 1,345
• Locations: 16 countries
• Sites: 117

Brief Summary

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.

Conditions

Partial Epilepsy

Outcome Measures

Primary Outcomes (1)

• Summary of Treatment-Emergent Adverse Events (TEAEs)

  TEAEs were defined as Adverse events (AEs) with onset on or after the start of study medication, up to last dose date of study medication + 14 days or onset before study medication and worsened after starting study medication, up to last dose date of study medication + 14 days.

  1 day to up to 215 weeks after first dose.

Other Outcomes (5)

• Vital Signs: Meeting Abnormal Criteria (Post-Baseline Measurement)

  1 day to up to 215 weeks after first dose.

• Exposure to Study Dose - Length (Weeks)

  1 day to up to 215 weeks after first dose.

• YKP3089 Plasma Levels (mcg/mL)

  Day 85 and Day 99 after first dose.

Study Arms (1)

YKP3089

EXPERIMENTAL

Multiple dose

Drug: YKP3089

Interventions

YKP3089 DRUG

see above

Also known as: other anti-epileptic drug (AED)

YKP3089

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Weight at least 30 kg
• 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.
• 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 and require additional AED therapy despite having been treated with at least one AED within approximately the last 2 years.
• Currently on stable antiepileptic treatment regimen:
• Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks prior to Visit 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.
• 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.
• 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.
• Ability to reach subject by telephone.
• Use of an acceptable form of birth control by female subjects of childbearing potential

You may not qualify if:

• 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.
• History of any drug-induced rash or hypersensitivity reaction.
• History of a first degree relative with a serious cutaneous drug-induced adverse reaction.
• 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
• Subjects taking phenytoin must not be taking phenobarbital or primidone; subjects taking phenobarbital must not be taking phenytoin or primidone
• Subjects taking concomitant AEDs other than phenytoin or phenobarbital, must not be taking phenytoin or phenobarbital or primidone
• Subjects with clinical evidence of phenytoin or phenobarbital toxicity
• A history of nonepileptic or psychogenic seizures
• Presence of only nonmotor simple partial seizures or primary generalized epilepsies
• Presence of Lennox-Gastaut syndrome
• Scheduled epilepsy surgery within 8 months after Visit 1
• Subjects implanted with or planning to have implantation of deep brain stimulator
• Pregnancy or lactation
• Any clinically significant laboratory abnormality that in the opinion of the investigator would exclude the subject from the study
• 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)

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (121)

Xen Institute

Phoenix, Arizona, 85004, United States

Location

Banner-University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

Arkansas Epilepsy Program

Little Rock, Arkansas, 72205, United States

Location

Kaiser Permanente - Southern California Medical Group

Anaheim, California, 92806, United States

Location

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Blue Sky Neurology

Englewood, Colorado, 80113, United States

Location

Bradenton Research Center Inc

Bradenton, Florida, 34205, United States

Location

NW FL Neurology Center

Gulf Breeze, Florida, 32561, United States

Location

Emory Brain Health Center

Atlanta, Georgia, 30329, United States

Location

Georgia Neurology and Sleep Medicine Associates

Suwanee, Georgia, 30024, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96814, United States

Location

Consultants In Epilepsy and Neurology PLLC

Boise, Idaho, 83702, United States

Location

MacFarland Clinic

Ames, Iowa, 50010, United States

Location

Maine Medical Partners Neurology

Scarborough, Maine, 04074, United States

Location

The John Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Klein, Pavel (Private Practice)

Bethesda, Maryland, 20817, United States

Location

Neurology Clinic PC

Waldorf, Maryland, 20603, United States

Location

Minneapolis Clinic of Neurology

Minneapolis, Minnesota, 55422, United States

Location

Comprehensive Epilepsy Care Center for Children and Adults PC

Chesterfield, Missouri, 63017, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Cincinnati, Physicians Company

Cincinnati, Ohio, 45219, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Providence Neurological Specialty Clinic

Portland, Oregon, 97213, United States

Location

Penn Epilepsy Center, Department of Neurology

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Austin Epilepsy Care Center

Austin, Texas, 78758, United States

Location

Hunt Regional Medical Partners

Greenville, Texas, 75034, United States

Location

Baylor Scott and White Research Institute

Temple, Texas, 76508, United States

Location

University of Virginia, School of Medicine

Charlottesville, Virginia, 22908, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98104, United States

Location

UW Medicine, Valley Medical Center

Seattle, Washington, 98122, United States

Location

Dean and St. Mary's Outpatient Center

Madison, Wisconsin, 53715, United States

Location

Centro de Educacion Medica e Investigaciones Clinicas (CEMIC)

Buenos Aires, Ciudad Autónoma de BuenosAires, C1431FWO, Argentina

Location

Hogar de Dia Casa Jesi

Buenos Aires, C1093AAS, Argentina

Location

Instituto de Neurociencias de Fundacion Favaloro

Buenos Aires, C1093AAS, Argentina

Location

Flinders Medical Centre

Bedford Park, 5042, Australia

Location

Eastern Health, Box Hill Hospital

Box Hill, 3128, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

Strategic Health Evaluators

Chatswood, 2067, Australia

Location

Monash Medical Centre

Clayton, 3168, Australia

Location

St. Vincent's Hospital Melbourne

Fitzroy, 3065, Australia

Location

Austin Health Melbourne Brain Centre

Heidelberg, 3084, Australia

Location

Royal Brisbane & Women's Hospital

Herston, 4029, Australia

Location

Alfred Health - The Alfred Hospital

Melbourne, 3004, Australia

Location

Melbourne Health (The Royal Melbourne Hospital)

Parkville, 3050, Australia

Location

Prince of Wales Hospital

Randwick, 2031, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

Multiprofile Hospital for Active Treatment Puls AD

Blagoevgrad, 2700, Bulgaria

Location

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

Sofia, 1113, Bulgaria

Location

First Multiprofile Hospital for Active Treatment- Sofia EAD

Sofia, 1142, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD

Sofia, 1431, Bulgaria

Location

Centro Neuropsicologia LTDA.

La Florida, Santiago Metropolitan, 8260094, Chile

Location

Complejo Asistencial Dr. Sotero Del Rio

Puente Alto, Santiago Metropolitan, 8207257, Chile

Location

Hospital Base Valdivia

Valdivia, 5090145, Chile

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Affidea Praha s.r.o.

Prague, 148 00, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel

Bielefeld, 33617, Germany

Location

University of Bonn, Department of Epileptology

Bonn, 53123, Germany

Location

Epilepsiezentrum Kork

Kehl, 77694, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Marburg, 35043, Germany

Location

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

Münster, 48149, Germany

Location

Országos Klinikai Idegtudományi Intézet

Budapest, 1145, Hungary

Location

Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz

Debrecen, 4031, Hungary

Location

Bacs Kiskun Megyei Korhaz

Kecskemét, 6000, Hungary

Location

Neurociencias Estudios Clinicos S.C.

Culiacán, 80020, Mexico

Location

Grupo Medico Camino S.C.

Mexico City, 03310, Mexico

Location

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

Mexico City, 14200, Mexico

Location

Centro de Investigacion Grupo Vitamagen

Monterrey, 64060, Mexico

Location

Clinical Research Institute S.C.

Tlalnepantla, 54055, Mexico

Location

Centrum Neurologii Krzysztof Selmaj

Lodz, Lódzkie, 90-324, Poland

Location

Centrum Leczenia Padaczki i Migreny

Krakow, Malopolski, 31-209, Poland

Location

Fundacja Epileptologii Prof Jerzego Majkowskiego

Warsaw, Masovian Voivodeship, 02-952, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, Masovian Voivodeship, 02-957, Poland

Location

Novo-Med Zielinski i wsp. Sp.J.

Katowice, Silesian Voivodeship, 40-650, Poland

Location

Copernicus Podmiot Leczniczy Sp. z o.o.

Gdansk, 80-803, Poland

Location

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

Moscow, 119991, Russia

Location

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

Perm, 614990, Russia

Location

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

Saint Petersburg, 192019, Russia

Location

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

Saint Petersburg, 197376, Russia

Location

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

Samara, 443095, Russia

Location

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

Smolensk, 214019, Russia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Institute of Mental Health

Belgrade, 11000, Serbia

Location

Military Medical Academy

Belgrade, 11000, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Dong-A University Hospital

Busan, 602-715, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, 41931, South Korea

Location

Severance Hospital at Yonsei University Health System

Seoul, 03722, South Korea

Location

Seoul National University Hospital

Seoul, 110744, South Korea

Location

Asan Medical Center

Seoul, 138736, South Korea

Location

Konkuk University Medical Center

Seoul, 143-729, South Korea

Location

Hospital Universitario Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Parque Tecnológico de la Salud

Granada, 18016, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

Location

Sahlgrenska University Hospital

Gothenburg, SE-41345, Sweden

Location

Faculty of Medicine, Chiang Mai University

Chiang Mai, Muang, 50200, Thailand

Location

King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University

Bangkok, Pathumwan, 10330, Thailand

Location

Municipal Institution Dnipropetrovsk Regional Clinical Hospital

Dnipro, 49005, Ukraine

Location

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

Kharkiv, 61068, Ukraine

Location

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

Kharkiv, 61103, Ukraine

Location

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

Lviv, 79010, Ukraine

Location

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

Odesa, Ukraine

Location

Municipal Non-Commercial Enterprise Odesa Regional Medical Center

Odesa, Ukraine

Location

Municipal Institution Odesa Regional Psychiatric Hospital #2

Oleksandrivka, 67513, Ukraine

Location

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

Ternopil, 46027, Ukraine

Location

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

Vinnytsia, 21005, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 38446341 DERIVED

• 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.

  PMID: 34633084 DERIVED

MeSH Terms

Conditions

Epilepsies, Partial

Interventions

Cenobamate

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: SK Life Science, Inc.

smisra@sklsi.com

402-835-5977

Study Officials

• Marc Kamin, MD

  SK Life Science, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: August 28, 2015
• Study Start: August 3, 2016
• Primary Completion: March 31, 2021
• Study Completion: February 7, 2022
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-04

Locations

BU (4); SE (1); UA (9); PL (6); ES (9); CZ (3); HU (3); AR (3); ME (5); KR (6); AU (12); DE (6); TH (2); RU (6); CL (3); US (39)