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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02535091
Other study ID # YKP3089C021
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date August 3, 2016
Est. completion date February 7, 2022

Study information

Verified date April 2024
Source SK Life Science, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

see above


Recruitment information / eligibility

Status Completed
Enrollment 1345
Est. completion date February 7, 2022
Est. primary completion date March 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
YKP3089
see above

Locations

Country Name City State
Argentina Centro de Educacion Medica e Investigaciones Clinicas (CEMIC) Buenos Aires Ciudad Autónoma De BuenosAires
Argentina Hogar de Dia Casa Jesi Buenos Aires
Argentina Instituto de Neurociencias de Fundacion Favaloro Buenos Aires
Australia Flinders Medical Centre Bedford Park
Australia Eastern Health, Box Hill Hospital Box Hill
Australia Royal Prince Alfred Hospital Camperdown
Australia Strategic Health Evaluators Chatswood
Australia Monash Medical Centre Clayton
Australia St. Vincent's Hospital Melbourne Fitzroy
Australia Austin Health Melbourne Brain Centre Heidelberg
Australia Royal Brisbane & Women's Hospital Herston
Australia Alfred Health - The Alfred Hospital Melbourne
Australia Melbourne Health (The Royal Melbourne Hospital) Parkville
Australia Prince of Wales Hospital Randwick
Australia Westmead Hospital Westmead
Bulgaria Multiprofile Hospital for Active Treatment Puls AD Blagoevgrad
Bulgaria First Multiprofile Hospital for Active Treatment- Sofia EAD Sofia
Bulgaria Multiprofile Hospital for Active Treatment of Neurology and Pschiatry "Sv. Naum" EAD Sofia
Bulgaria University Multiprofile Hospital for Active Treatment Aleksandrovska EAD Sofia
Chile Centro Neuropsicologia LTDA. La Florida Santiago
Chile Complejo Asistencial Dr. Sotero Del Rio Puente Alto Santiago
Chile Hospital Base Valdivia Valdivia
Czechia Fakultni nemocnice u sv. Anny v Brne Brno
Czechia Affidea Praha s.r.o. Prague
Czechia Fakultni nemocnice v Motole Praha 5
Germany Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel Bielefeld
Germany University of Bonn, Department of Epileptology Bonn
Germany Epilepsiezentrum Kork Kehl
Germany Universitätsmedizin der Johannes Gutenberg-Universität Mainz Mainz
Germany Universitätsklinikum Gießen und Marburg GmbH Marburg
Germany Universitätsklinikum Münster, Klinik fur Neurologie mit Institut fur Translationale Neurologie-Epileptologie Münster
Hungary Országos Klinikai Idegtudományi Intézet Budapest
Hungary Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz Debrecen
Hungary Bacs Kiskun Megyei Korhaz Kecskemét
Korea, Republic of Dong-A University Hospital Busan
Korea, Republic of Keimyung University Dongsan Hospital Daegu
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Konkuk University Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital at Yonsei University Health System Seoul
Mexico Grupo Medico Camino S.C. Ciudad de Mexico
Mexico Human Science Research Trials S. de R.L. de C.V. Ciudad de Mexico
Mexico Neurociencias Estudios Clinicos S.C. Culiacán
Mexico Centro de Investigacion Grupo Vitamagen Monterrey
Mexico Clinical Research Institute S.C. Tlanepantla De Baz
Poland Copernicus Podmiot Leczniczy Sp. z o.o. Gdansk
Poland Novo-Med Zielinski i wsp. Sp.J. Katowice Slaskie
Poland Centrum Leczenia Padaczki i Migreny Kraków Malopolski
Poland Centrum Neurologii Krzysztof Selmaj Lódz Lódzkie
Poland Fundacja Epileptologii Prof Jerzego Majkowskiego Warszawa Mazowieckie
Poland Instytut Psychiatrii i Neurologii Warszawa Mazowieckie
Russian Federation FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.P. Serbskiy of MoH of RF Moscow
Russian Federation SBHI of Perm Region, Perm Territorial Clinical Hospital, Centre for Multiple Sclerosis Perm
Russian Federation FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev of MoH of RF Saint Petersburg
Russian Federation FSBI of Science, Institute of Human Brain n.a. N.P. Bekhtereva of RAN, Laboratory of Stereotaxic Methods Saint Petersburg
Russian Federation SBHI Samara Regional Clinical Hospital n.a. V.D. Seredavin, Neurology and Neurosurgery Departments Samara
Russian Federation SBGEI of HPE Smolensk State Medical University of MoH of RF, Chair Neurology and Neurosurgery Smolensk
Serbia Clinical Center of Serbia Belgrade
Serbia Institute of Mental Health Belgrade
Serbia Military Medical Academy Belgrade
Serbia Clinical Center Kragujevac Kragujevac
Spain Hospital Universitario Germans Trias i Pujol Badalona
Spain Hospital del Mar Barcelona
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Hospital Parque Tecnológico de la Salud Granada
Spain Hospital Ruber Internacional Madrid
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital Universitario Clinico San Carlos Madrid
Spain Hospital Universitario Fundacion Jimenez Diaz Madrid
Spain Hospital Universitario y Politecnico La Fe Valencia
Sweden Sahlgrenska University Hospital Göteborg
Thailand King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University Bangkok Pathumwan
Thailand Faculty of Medicine, Chiang Mai University Chiang Mai Muang
Ukraine Municipal Institution Dnipropetrovsk Regional Clinical Hospital Dnipro
Ukraine Communal Non-Commercial Enterprise of Kharkiv Regional Counsil "Regional clinical psychiatric hospital #3" Kharkiv
Ukraine Kharkiv Railway Clinical Hospital #1 of the Health Center Branch of JSC Ukrzaliznytsia Kharkiv
Ukraine Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital" Lviv
Ukraine Municipal Non-Commercial Enterprise Odesa Regional Medical Center Odesa
Ukraine Municipal Non-Commercial Enterprise Odesa Regional Medical Center for Mental Health of Odessa Regional Council Odesa
Ukraine Municipal Institution Odesa Regional Psychiatric Hospital #2 Oleksandrivka
Ukraine Municipal Non-Commercial Enterprise "Ternopil Regional Clinical Psychoneurological Hospital" of Ternopil Regional Council Ternopil
Ukraine Communal Non-profit Enterprise "Vinnytsia Regional Clinical Psycho-Neurological Hospital" Vinnytsia
United States MacFarland Clinic Ames Iowa
United States Kaiser Permanente - Southern California Medical Group Anaheim California
United States Emory Brain Health Center Atlanta Georgia
United States Austin Epilepsy Care Center Austin Texas
United States The John Hopkins University School of Medicine Baltimore Maryland
United States Klein, Pavel (Private Practice) Bethesda Maryland
United States Consultants In Epilepsy and Neurology PLLC Boise Idaho
United States Bradenton Research Center Inc Bradenton Florida
United States Montefiore Medical Center Bronx New York
United States Medical University of South Carolina Charleston South Carolina
United States University of Virginia, School of Medicine Charlottesville Virginia
United States Comprehensive Epilepsy Care Center for Children and Adults PC Chesterfield Missouri
United States University of Cincinnati, Physicians Company Cincinnati Ohio
United States Riverside Methodist Hospital Columbus Ohio
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States Blue Sky Neurology Englewood Colorado
United States Neuro Pain Medical Center Fresno California
United States Hunt Regional Medical Partners Greenville Texas
United States NW FL Neurology Center Gulf Breeze Florida
United States Northeast Regional Epilepsy Group Hackensack New Jersey
United States Hawaii Pacific Neuroscience Honolulu Hawaii
United States Arkansas Epilepsy Program Little Rock Arkansas
United States Dean and St. Mary's Outpatient Center Madison Wisconsin
United States Minneapolis Clinic of Neurology Minneapolis Minnesota
United States Vanderbilt University Medical Center Nashville Tennessee
United States NYU Langone Medical Center New York New York
United States Penn Epilepsy Center, Department of Neurology Philadelphia Pennsylvania
United States Thomas Jefferson University Comprehensive Epilepsy Center Philadelphia Pennsylvania
United States Banner-University Medical Center Phoenix Phoenix Arizona
United States Xen Institute Phoenix Arizona
United States Providence Neurological Specialty Clinic Portland Oregon
United States University of Rochester Medical Center Rochester New York
United States California Pacific Medical Center San Francisco California
United States Maine Medical Partners Neurology Scarborough Maine
United States University of Washington School of Medicine Seattle Washington
United States UW Medicine, Valley Medical Center Seattle Washington
United States Georgia Neurology and Sleep Medicine Associates Suwanee Georgia
United States Baylor Scott and White Research Institute Temple Texas
United States Neurology Clinic PC Waldorf Maryland

Sponsors (1)

Lead Sponsor Collaborator
SK Life Science, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Chile,  Czechia,  Germany,  Hungary,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Serbia,  Spain,  Sweden,  Thailand,  Ukraine, 

Outcome

Type Measure Description Time frame Safety issue
Other Vital Signs: Meeting Abnormal Criteria (Post-Baseline Measurement) Subjects with At Least 1 Post-Baseline Measurement Meeting Abnormal Criteria. Changes in systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature, weight, and height in each safety evaluable group were small and not clinically meaningful. 1 day to up to 215 weeks after first dose.
Other Exposure to Study Dose - Length (Weeks) Exposure to Study Dose was measured in Safety Population. Modal daily dose defined as the dose taken the most days during the reporting phase or study; in case of ties, modal dose was defined as the highest dose level between the two doses in the tie. 1 day to up to 215 weeks after first dose.
Other YKP3089 Plasma Levels (mcg/mL) At Visit 8 and Visit 9, 2 blood samples were collected for the determination of YKP3089 plasma levels (YKP3089 and concomitant AED doses must have been stable for 2 weeks prior to these visits), at arrival and 30 minutes to 4 hours after the most recent dose.
Plasma levels of phenytoin and phenobarbital were stable during the titration. The endpoint values are based on pharmacokinetic (PK) population.
Day 85 and Day 99 after first dose.
Other Exposure to Study Dose - Length (Months) Exposure to Study Dose was measured in Safety Population. Modal daily dose defined as the dose taken the most days during the reporting phase or study; in case of ties, modal dose was defined as the highest dose level between the two doses in the tie. 1 day to up to 215 weeks after first dose.
Other Average Exposure to Study Dose Exposure to Study Dose was measured in Safety Population. Modal daily dose defined as the dose taken the most days during the reporting phase or study; in case of ties, modal dose was defined as the highest dose level between the two doses in the tie. 1 day to up to 215 weeks after first dose.
Primary 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.
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