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

Sponsor
SK Life Science, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02535091
Collaborator
(none)
1,345
Enrollment
121
Locations
1
Arm
66.2
Actual Duration (Months)
11.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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 other than phenytoin and phenobarbital to further investigate long-term safety.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

see above

Study Design

Study Type:
Interventional
Actual Enrollment :
1345 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label, Multicenter, Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
Actual Study Start Date :
Aug 3, 2016
Actual Primary Completion Date :
Mar 31, 2021
Actual Study Completion Date :
Feb 7, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: YKP3089

Multiple dose

Drug: YKP3089
see above
Other Names:
  • other AEDs

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Evaluate the pharmacokinetics of YKP3089 and concomitant Antiepileptic Drugs (AEDs) [12 weeks]

      Change from baseline of trough plasma concentrations of YKP3089 and concomitant AEDs

    2. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [12 months. After 12 months, subjects re-evaluated and may have continued at the discretion of investigator]

      All observed or volunteered AEs and SAEs regardless of suspected causal relationship to the investigational product to be reported

    3. Percentage of Participants With Laboratory Test Abnormalities (Hematology) [12 months. After 12 months, subjects re-evaluated and may have continued at the discretion of investigator]

      Hematology data will be analyzed by central laboratories.

    4. Percentage of Participants With Laboratory Test Abnormalities (Chemistry) [12 months. After 12 months, subjects re-evaluated and may have continued at the discretion of investigator]

      Chemistry data will be analyzed by central laboratories

    5. Percentage of Participants With Laboratory Test Abnormalities (Urinalysis) [12 months. After 12 months, subjects re-evaluated and may have continued at the discretion of investigator]

      Urinalysis data will be analyzed by central laboratories

    6. Percentage of Participants With Vital Sign Results of Potential Clinical Importance [12 months. After 12 months, subjects re-evaluated and may have continued at the discretion of investigator]

      Vital signs include sitting blood pressure, respiration rate, heart rate and temperature. Potential clinical importance to be determined according to investigator clinical judgement

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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 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:

    7. Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks prior to Visit 2

    8. 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.

    9. 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.

    10. 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.

    11. Ability to reach subject by telephone.

    12. 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 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 VPA

    27. 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.

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Xen Institute Phoenix Arizona United States 85004
    2 Banner-University Medical Center Phoenix Phoenix Arizona United States 85006
    3 Arkansas Epilepsy Program Little Rock Arkansas United States 72205
    4 Kaiser Permanente - Southern California Medical Group Anaheim California United States 92806
    5 Neuro Pain Medical Center Fresno California United States 93710
    6 California Pacific Medical Center San Francisco California United States 94115
    7 Blue Sky Neurology Englewood Colorado United States 80113
    8 Bradenton Research Center Inc Bradenton Florida United States 34205
    9 NW FL Neurology Center Gulf Breeze Florida United States 32561
    10 Emory Brain Health Center Atlanta Georgia United States 30329
    11 Georgia Neurology and Sleep Medicine Associates Suwanee Georgia United States 30024
    12 Hawaii Pacific Neuroscience Honolulu Hawaii United States 96814
    13 Consultants In Epilepsy and Neurology PLLC Boise Idaho United States 83702
    14 MacFarland Clinic Ames Iowa United States 50010
    15 Maine Medical Partners Neurology Scarborough Maine United States 04074
    16 The John Hopkins University School of Medicine Baltimore Maryland United States 21287
    17 Klein, Pavel (Private Practice) Bethesda Maryland United States 20817
    18 Neurology Clinic PC Waldorf Maryland United States 20603
    19 Minneapolis Clinic of Neurology Minneapolis Minnesota United States 55422
    20 Comprehensive Epilepsy Care Center for Children and Adults PC Chesterfield Missouri United States 63017
    21 Northeast Regional Epilepsy Group Hackensack New Jersey United States 07601
    22 Montefiore Medical Center Bronx New York United States 10467
    23 NYU Langone Medical Center New York New York United States 10016
    24 University of Rochester Medical Center Rochester New York United States 14642
    25 University of Cincinnati, Physicians Company Cincinnati Ohio United States 45219
    26 The Ohio State University Wexner Medical Center Columbus Ohio United States 43210
    27 Riverside Methodist Hospital Columbus Ohio United States 43214
    28 Providence Neurological Specialty Clinic Portland Oregon United States 97213
    29 Penn Epilepsy Center, Department of Neurology Philadelphia Pennsylvania United States 19104
    30 Thomas Jefferson University Comprehensive Epilepsy Center Philadelphia Pennsylvania United States 19107
    31 Medical University of South Carolina Charleston South Carolina United States 29425
    32 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    33 Austin Epilepsy Care Center Austin Texas United States 78758
    34 Hunt Regional Medical Partners Greenville Texas United States 75034
    35 Baylor Scott and White Research Institute Temple Texas United States 76508
    36 University of Virginia, School of Medicine Charlottesville Virginia United States 22908
    37 University of Washington School of Medicine Seattle Washington United States 98104
    38 UW Medicine, Valley Medical Center Seattle Washington United States 98122
    39 Dean and St. Mary's Outpatient Center Madison Wisconsin United States 53715
    40 Centro de Educacion Medica e Investigaciones Clinicas (CEMIC) Buenos Aires Ciudad Autónoma De BuenosAires Argentina C1431FWO
    41 Hogar de Dia Casa Jesi Buenos Aires Argentina C1093AAS
    42 Instituto de Neurociencias de Fundacion Favaloro Buenos Aires Argentina C1093AAS
    43 Flinders Medical Centre Bedford Park Australia 5042
    44 Eastern Health, Box Hill Hospital Box Hill Australia 3128
    45 Royal Prince Alfred Hospital Camperdown Australia 2050
    46 Strategic Health Evaluators Chatswood Australia 2067
    47 Monash Medical Centre Clayton Australia 3168
    48 St. Vincent's Hospital Melbourne Fitzroy Australia 3065
    49 Austin Health Melbourne Brain Centre Heidelberg Australia 3084
    50 Royal Brisbane & Women's Hospital Herston Australia 4029
    51 Alfred Health - The Alfred Hospital Melbourne Australia 3004
    52 Melbourne Health (The Royal Melbourne Hospital) Parkville Australia 3050
    53 Prince of Wales Hospital Randwick Australia 2031
    54 Westmead Hospital Westmead Australia 2145
    55 Multiprofile Hospital for Active Treatment Puls AD Blagoevgrad Bulgaria 2700
    56 Multiprofile Hospital for Active Treatment of Neurology and Pschiatry "Sv. Naum" EAD Sofia Bulgaria 1113
    57 First Multiprofile Hospital for Active Treatment- Sofia EAD Sofia Bulgaria 1142
    58 University Multiprofile Hospital for Active Treatment Aleksandrovska EAD Sofia Bulgaria 1431
    59 Centro Neuropsicologia LTDA. La Florida Santiago Chile 8260094
    60 Complejo Asistencial Dr. Sotero Del Rio Puente Alto Santiago Chile 8207257
    61 Hospital Base Valdivia Valdivia Chile 5090145
    62 Fakultni nemocnice u sv. Anny v Brne Brno Czechia 656 91
    63 Affidea Praha s.r.o. Prague Czechia 148 00
    64 Fakultni nemocnice v Motole Praha 5 Czechia 150 06
    65 Krankenhaus Mara gGmbH - Epilepsiezentrum Bethel Bielefeld Germany 33617
    66 University of Bonn, Department of Epileptology Bonn Germany 53123
    67 Epilepsiezentrum Kork Kehl Germany 77694
    68 Universitätsmedizin der Johannes Gutenberg-Universität Mainz Mainz Germany 55131
    69 Universitätsklinikum Gießen und Marburg GmbH Marburg Germany 35043
    70 Universitätsklinikum Münster, Klinik fur Neurologie mit Institut fur Translationale Neurologie-Epileptologie Münster Germany 48149
    71 Országos Klinikai Idegtudományi Intézet Budapest Hungary 1145
    72 Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz Debrecen Hungary 4031
    73 Bacs Kiskun Megyei Korhaz Kecskemét Hungary 6000
    74 Dong-A University Hospital Busan Korea, Republic of 602-715
    75 Keimyung University Dongsan Hospital Daegu Korea, Republic of 41931
    76 Severance Hospital at Yonsei University Health System Seoul Korea, Republic of 03722
    77 Seoul National University Hospital Seoul Korea, Republic of 110744
    78 Asan Medical Center Seoul Korea, Republic of 138736
    79 Konkuk University Medical Center Seoul Korea, Republic of 143-729
    80 Grupo Medico Camino S.C. Ciudad de Mexico Mexico 03310
    81 Human Science Research Trials S. de R.L. de C.V. Ciudad de Mexico Mexico 14200
    82 Neurociencias Estudios Clinicos S.C. Culiacán Mexico 80020
    83 Centro de Investigacion Grupo Vitamagen Monterrey Mexico 64060
    84 Clinical Research Institute S.C. Tlanepantla De Baz Mexico 54055
    85 Centrum Neurologii Krzysztof Selmaj Łódź Lódzkie Poland 90-324
    86 Centrum Leczenia Padaczki i Migreny Kraków Malopolski Poland 31-209
    87 Fundacja Epileptologii Prof Jerzego Majkowskiego Warszawa Mazowieckie Poland 02-952
    88 Instytut Psychiatrii i Neurologii Warszawa Mazowieckie Poland 02-957
    89 Novo-Med Zielinski i wsp. Sp.J. Katowice Slaskie Poland 40-650
    90 Copernicus Podmiot Leczniczy Sp. z o.o. Gdańsk Poland 80-803
    91 FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.P. Serbskiy of MoH of RF Moscow Russian Federation 119991
    92 SBHI of Perm Region, Perm Territorial Clinical Hospital, Centre for Multiple Sclerosis Perm Russian Federation 614990
    93 FSBI National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev of MoH of RF Saint Petersburg Russian Federation 192019
    94 FSBI of Science, Institute of Human Brain n.a. N.P. Bekhtereva of RAN, Laboratory of Stereotaxic Methods Saint Petersburg Russian Federation 197376
    95 SBHI Samara Regional Clinical Hospital n.a. V.D. Seredavin, Neurology and Neurosurgery Departments Samara Russian Federation 443095
    96 SBGEI of HPE Smolensk State Medical University of MoH of RF, Chair Neurology and Neurosurgery Smolensk Russian Federation 214019
    97 Clinical Center of Serbia Belgrade Serbia 11000
    98 Institute of Mental Health Belgrade Serbia 11000
    99 Military Medical Academy Belgrade Serbia 11000
    100 Clinical Center Kragujevac Kragujevac Serbia 34000
    101 Hospital Universitario Germans Trias i Pujol Badalona Spain 08916
    102 Hospital del Mar Barcelona Spain 08003
    103 Hospital Universitario Vall d'Hebron Barcelona Spain 08035
    104 Hospital Parque Tecnológico de la Salud Granada Spain 18016
    105 Hospital Ruber Internacional Madrid Spain 28034
    106 Hospital Universitario Clinico San Carlos Madrid Spain 28040
    107 Hospital Universitario Fundacion Jimenez Diaz Madrid Spain 28040
    108 Hospital Universitario 12 de Octubre Madrid Spain 28041
    109 Hospital Universitario y Politecnico La Fe Valencia Spain 46026
    110 Sahlgrenska University Hospital Göteborg Sweden SE-41345
    111 Faculty of Medicine, Chiang Mai University Chiang Mai Muang Thailand 50200
    112 King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University Bangkok Pathumwan Thailand 10330
    113 Municipal Institution Dnipropetrovsk Regional Clinical Hospital Dnipro Ukraine 49005
    114 Communal Non-Commercial Enterprise of Kharkiv Regional Counsil "Regional clinical psychiatric hospital #3" Kharkiv Ukraine 61068
    115 Kharkiv Railway Clinical Hospital #1 of the Health Center Branch of JSC Ukrzaliznytsia Kharkiv Ukraine 61103
    116 Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital" Lviv Ukraine 79010
    117 Municipal Non-Commercial Enterprise Odesa Regional Medical Center for Mental Health of Odessa Regional Council Odesa Ukraine
    118 Municipal Non-Commercial Enterprise Odesa Regional Medical Center Odesa Ukraine
    119 Municipal Institution Odesa Regional Psychiatric Hospital #2 Oleksandrivka Ukraine 67513
    120 Municipal Non-Commercial Enterprise "Ternopil Regional Clinical Psychoneurological Hospital" of Ternopil Regional Council Ternopil Ukraine 46027
    121 Communal Non-profit Enterprise "Vinnytsia Regional Clinical Psycho-Neurological Hospital" Vinnytsia Ukraine 21005

    Sponsors and Collaborators

    • SK Life Science, Inc.

    Investigators

    • Study Director: Marc Kamin, MD, SK Life Science, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SK Life Science, Inc.
    ClinicalTrials.gov Identifier:
    NCT02535091
    Other Study ID Numbers:
    • YKP3089C021
    First Posted:
    Aug 28, 2015
    Last Update Posted:
    Feb 15, 2022
    Last Verified:
    Feb 1, 2022
    Additional relevant MeSH terms:
    Seizures
    Epilepsies, Partial
    Cenobamate

    Study Results

    No Results Posted as of Feb 15, 2022