Back to resultsA Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
Primary Purpose
Partial Epilepsy
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
YKP3089
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Partial Epilepsy
Eligibility Criteria
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
Sites / Locations
- St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics
- Clinical Trials, Inc.
- Kaiser Permanente, Department of Neurology
- Neuro-Pain Medical Center
- West Los Angeles VA Medical Center, Clinical Research Center
- Neuroresearch, Inc. - Torrance
- Neuroresearch II, Inc.
- Bradenton Research Center, Inc.
- Lovelace Scientific Resources, Inc.
- Consultants in Epilepsy & Neurology, PLLC
- Johns Hopkins University
- Mid-Atlantic Epilepsy and Sleep Center
- Neurology Clinic PC
- The Comprehensive Epilepsy Care Center for Children and Adults
- Northeast Regional Epilepsy Group
- NYU Comprehensive Epilepsy Center
- The Neurological Institute, PA
- Thomas Jefferson Comprehensive Epilepsy Center
- Vanderbilt Epilepsy Clinic
- Austin Epilepsy Care Center
- University of Virginia Comprehensive Epilepsy Program
- Institute of Neurological Sciences, Prince of Wales Hospital
- Monash Medical Centre
- St. Vincent's Hospital (Melbourne)
- Epilepsy Research Centre, Melbourne Brain Centre
- The Royal Melbourne Hospital
- University Multiprofile Hpspital for Active Treatment "Sveti Georgi" EAD, Clinic of Neurological Diseases
- "First Multiprofile Hospital for Active Treatment - Sofia" EAD, Neurology Clinic
- University of Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD, Clinic of Neurological Diseases
- Fakultní nemocnice Ostrava, Neurologická klinika
- Mediscan Group, s.r.o
- Fakultni nemocnice v Motole, Neurologická klinika
- CHU - Service Neurophysiologie Clinique
- Hôpital Central - CHU de Nancy - Service de Neurologie
- Epilepsiezentrum Berlin- Bradenburg, Epilepsieklinik "Tabor"
- Krankenhaus Mara gGmbH, Epilepsiezentrum Bethel
- Epilepsiezentrum Kork
- Országos Klinikai Idegtudományi Intézet
- Department of Neurology, Hadassah University Hospital Ein Kerem, Kiryat Hadassah
- Western Galilee Hospital, Department of Neurology
- The Chaim Sheba Medical Center, Department of Neurology
- Dong-A University Hospital
- Seoul National University Hospital
- Samsung Medical Center
- Asan Medical Center
- Konkuk University Medical Center
- M.A. - LEK A.M. Maciejowscy S.C. Centrum Terapii SM
- NOVO-MED Zielinski I Wspolnicy Spolka Jawna
- NZOZ Centrum Medyczne "Dendryt"
- Fundacja Epileptologii profesora Jerzego Majkowskiego
- Instytut Psychaitrii I Neurologii, II Klinika Neurologiczna
- Roceanu Adina Maria Neurology Individual Medical Center
- Sapiens Medical Center SRL
- Clinical of Neurology, Clinical Center of Serbia
- Institute of Mental Health
- Clinical Hospital Center Kragujevac
- Hospital Universitario San Cecilio - Servicio de Neurologia
- Hospital Ruber Internacional - Programa Epilepsia
- Fundación Jiminez Diaz-Servicio de Neurologia
- Hospital Clinico Universitario San Carlos, Serv. Neurologia
- Hospital Universitario y Politecnico La Fe - Servicio Neurologia
- Srinagarind Hospital
- 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"
- TDC "Epilepsy" based on Department #19 of Kiev Territorial Medical Association "Psychiatry"
- 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
- MI "Odessa Regional Clinical Hospital," Neurological and Neurosurgical Center based on Neurosurgery Department
- Department #2 of Regional Clinical Center of Neurosurgery and Neurology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
YKP3089 Low Dose
YKP3089 Medium Dose
YKP3089 High Dose
Arm Description
Placebo
YKP3089 Low Dose
YKP3089 Medium Dose
YKP3089 High Dose
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
Percent change in complex partial and/or secondarily generalized and/or simple partial motor seizure frequency per 28 days (average 28-day seizure rate) in each treatment group during the double-blind period relative to the pretreatment baseline.
Secondary Outcome Measures
50% Responder Rate
Percentage of patients achieving a 50% or more reduction from baseline in partial seizure frequency during the double-blind treatment period
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01866111
Brief Title
A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
Official Title
A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Response Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures, With Optional Open-Label Extension
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 31, 2013 (Actual)
Primary Completion Date
April 5, 2021 (Actual)
Study Completion Date
October 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SK Life Science, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Partial Epilepsy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
437 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
YKP3089 Low Dose
Arm Type
Experimental
Arm Description
YKP3089 Low Dose
Arm Title
YKP3089 Medium Dose
Arm Type
Experimental
Arm Description
YKP3089 Medium Dose
Arm Title
YKP3089 High Dose
Arm Type
Experimental
Arm Description
YKP3089 High Dose
Intervention Type
Drug
Intervention Name(s)
YKP3089
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
Description
Percent change in complex partial and/or secondarily generalized and/or simple partial motor seizure frequency per 28 days (average 28-day seizure rate) in each treatment group during the double-blind period relative to the pretreatment baseline.
Time Frame
baseline and 18 weeks
Secondary Outcome Measure Information:
Title
50% Responder Rate
Description
Percentage of patients achieving a 50% or more reduction from baseline in partial seizure frequency during the double-blind treatment period
Time Frame
18 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Clinical Trials, Inc.
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Kaiser Permanente, Department of Neurology
City
Anaheim
State/Province
California
ZIP/Postal Code
92806
Country
United States
Facility Name
Neuro-Pain Medical Center
City
Fresno
State/Province
California
ZIP/Postal Code
93710
Country
United States
Facility Name
West Los Angeles VA Medical Center, Clinical Research Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
Neuroresearch, Inc. - Torrance
City
Torrance
State/Province
California
ZIP/Postal Code
90505
Country
United States
Facility Name
Neuroresearch II, Inc.
City
Ventura
State/Province
California
ZIP/Postal Code
93003
Country
United States
Facility Name
Bradenton Research Center, Inc.
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34205
Country
United States
Facility Name
Lovelace Scientific Resources, Inc.
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34233
Country
United States
Facility Name
Consultants in Epilepsy & Neurology, PLLC
City
Boise
State/Province
Idaho
ZIP/Postal Code
83702
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Mid-Atlantic Epilepsy and Sleep Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Neurology Clinic PC
City
Waldorf
State/Province
Maryland
ZIP/Postal Code
20603
Country
United States
Facility Name
The Comprehensive Epilepsy Care Center for Children and Adults
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63017
Country
United States
Facility Name
Northeast Regional Epilepsy Group
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
NYU Comprehensive Epilepsy Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
The Neurological Institute, PA
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Thomas Jefferson Comprehensive Epilepsy Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Vanderbilt Epilepsy Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Austin Epilepsy Care Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Facility Name
University of Virginia Comprehensive Epilepsy Program
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Institute of Neurological Sciences, Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
St. Vincent's Hospital (Melbourne)
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Epilepsy Research Centre, Melbourne Brain Centre
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
The Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
University Multiprofile Hpspital for Active Treatment "Sveti Georgi" EAD, Clinic of Neurological Diseases
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
"First Multiprofile Hospital for Active Treatment - Sofia" EAD, Neurology Clinic
City
Sofia
ZIP/Postal Code
1142
Country
Bulgaria
Facility Name
University of Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD, Clinic of Neurological Diseases
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
Fakultní nemocnice Ostrava, Neurologická klinika
City
Ostrava
ZIP/Postal Code
70825
Country
Czechia
Facility Name
Mediscan Group, s.r.o
City
Praha 4
ZIP/Postal Code
148 00
Country
Czechia
Facility Name
Fakultni nemocnice v Motole, Neurologická klinika
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
CHU - Service Neurophysiologie Clinique
City
Dijon Cedex
ZIP/Postal Code
21079
Country
France
Facility Name
Hôpital Central - CHU de Nancy - Service de Neurologie
City
Nancy
ZIP/Postal Code
5400
Country
France
Facility Name
Epilepsiezentrum Berlin- Bradenburg, Epilepsieklinik "Tabor"
City
Bernau bei Berlin
ZIP/Postal Code
16321
Country
Germany
Facility Name
Krankenhaus Mara gGmbH, Epilepsiezentrum Bethel
City
Bielefeld
ZIP/Postal Code
33617
Country
Germany
Facility Name
Epilepsiezentrum Kork
City
Kehl
ZIP/Postal Code
77694
Country
Germany
Facility Name
Országos Klinikai Idegtudományi Intézet
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
Department of Neurology, Hadassah University Hospital Ein Kerem, Kiryat Hadassah
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Western Galilee Hospital, Department of Neurology
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
The Chaim Sheba Medical Center, Department of Neurology
City
Ramat-Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Dong-A University Hospital
City
Busan
ZIP/Postal Code
602715
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110744
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135710
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138736
Country
Korea, Republic of
Facility Name
Konkuk University Medical Center
City
Seoul
ZIP/Postal Code
143729
Country
Korea, Republic of
Facility Name
M.A. - LEK A.M. Maciejowscy S.C. Centrum Terapii SM
City
Katowice
ZIP/Postal Code
40-595
Country
Poland
Facility Name
NOVO-MED Zielinski I Wspolnicy Spolka Jawna
City
Katowice
ZIP/Postal Code
40-650
Country
Poland
Facility Name
NZOZ Centrum Medyczne "Dendryt"
City
Katowice
ZIP/Postal Code
40-662
Country
Poland
Facility Name
Fundacja Epileptologii profesora Jerzego Majkowskiego
City
Warsaw
ZIP/Postal Code
02-952
Country
Poland
Facility Name
Instytut Psychaitrii I Neurologii, II Klinika Neurologiczna
City
Warszawa
ZIP/Postal Code
02-957
Country
Poland
Facility Name
Roceanu Adina Maria Neurology Individual Medical Center
City
Bucharest
ZIP/Postal Code
010042
Country
Romania
Facility Name
Sapiens Medical Center SRL
City
Bucharest
ZIP/Postal Code
011635
Country
Romania
Facility Name
Clinical of Neurology, Clinical Center of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Institute of Mental Health
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Clinical Hospital Center Kragujevac
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
Hospital Universitario San Cecilio - Servicio de Neurologia
City
Granada
ZIP/Postal Code
18012
Country
Spain
Facility Name
Hospital Ruber Internacional - Programa Epilepsia
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Fundación Jiminez Diaz-Servicio de Neurologia
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Clinico Universitario San Carlos, Serv. Neurologia
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario y Politecnico La Fe - Servicio Neurologia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Srinagarind Hospital
City
Na Muang
State/Province
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
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"
City
Kharkiv
ZIP/Postal Code
61103
Country
Ukraine
Facility Name
TDC "Epilepsy" based on Department #19 of Kiev Territorial Medical Association "Psychiatry"
City
Kyiv
ZIP/Postal Code
04080
Country
Ukraine
Facility Name
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
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Facility Name
MI "Odessa Regional Clinical Hospital," Neurological and Neurosurgical Center based on Neurosurgery Department
City
Odessa
ZIP/Postal Code
65025
Country
Ukraine
Facility Name
Department #2 of Regional Clinical Center of Neurosurgery and Neurology
City
Uzhgorod
ZIP/Postal Code
88018
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
35705501
Citation
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 Jun 15;99(10):e989-98. doi: 10.1212/WNL.0000000000200792. Online ahead of print.
Results Reference
derived
PubMed Identifier
33662894
Citation
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.
Results Reference
derived
PubMed Identifier
31734103
Citation
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. Erratum In: Lancet Neurol. 2020 Mar;19(3):e3.
Results Reference
derived
PubMed Identifier
25769377
Citation
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.
Results Reference
derived
Learn more about this trial
A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
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