Clinical trial NCT01866111: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Partial Epilepsy
Lead sponsor: SK Life Science, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-31
Enrollment: 437
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
timeFrame: baseline and 18 weeks
Secondary outcomes:
measure: 50% Responder Rate
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials, Inc.
state: Arkansas
city: Anaheim
country: United States
facility: Kaiser Permanente, Department of Neurology
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Medical Center, Clinical Research Center
state: California
city: Torrance
country: United States
facility: Neuroresearch, Inc. - Torrance
state: California
city: Ventura
country: United States
facility: Neuroresearch II, Inc.
state: California
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc.
state: Florida
city: Sarasota
country: United States
facility: Lovelace Scientific Resources, Inc.
state: Florida
city: Boise
country: United States
facility: Consultants in Epilepsy & Neurology, PLLC
state: Idaho
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Waldorf
country: United States
facility: Neurology Clinic PC
state: Maryland
city: Saint Louis
country: United States
facility: The Comprehensive Epilepsy Care Center for Children and Adults
state: Missouri
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: New York
country: United States
facility: NYU Comprehensive Epilepsy Center
state: New York
city: Charlotte
country: United States
facility: The Neurological Institute, PA
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson Comprehensive Epilepsy Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Epilepsy Clinic
state: Tennessee
city: Austin
country: United States
facility: Austin Epilepsy Care Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Epilepsy Program
state: Virginia
city: Randwick
country: Australia
facility: Institute of Neurological Sciences, Prince of Wales Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital (Melbourne)
state: Victoria
city: Heidelberg
country: Australia
facility: Epilepsy Research Centre, Melbourne Brain Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hpspital for Active Treatment "Sveti Georgi" EAD, Clinic of Neurological Diseases
city: Sofia
country: Bulgaria
facility: "First Multiprofile Hospital for Active Treatment - Sofia" EAD, Neurology Clinic
city: Sofia
country: Bulgaria
facility: University of Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD, Clinic of Neurological Diseases
city: Ostrava
country: Czechia
facility: Fakultní nemocnice Ostrava, Neurologická klinika
city: Praha 4
country: Czechia
facility: Mediscan Group, s.r.o
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole, Neurologická klinika
city: Dijon Cedex
country: France
facility: CHU - Service Neurophysiologie Clinique
city: Nancy
country: France
facility: Hôpital Central - CHU de Nancy - Service de Neurologie
city: Bernau bei Berlin
country: Germany
facility: Epilepsiezentrum Berlin- Bradenburg, Epilepsieklinik "Tabor"
city: Bielefeld
country: Germany
facility: Krankenhaus Mara gGmbH, Epilepsiezentrum Bethel
city: Kehl
country: Germany
facility: Epilepsiezentrum Kork
city: Budapest
country: Hungary
facility: Országos Klinikai Idegtudományi Intézet
city: Jerusalem
country: Israel
facility: Department of Neurology, Hadassah University Hospital Ein Kerem, Kiryat Hadassah
city: Nahariya
country: Israel
facility: Western Galilee Hospital, Department of Neurology
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center, Department of Neurology
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Katowice
country: Poland
facility: M.A. - LEK A.M. Maciejowscy S.C. Centrum Terapii SM
city: Katowice
country: Poland
facility: NOVO-MED Zielinski I Wspolnicy Spolka Jawna
city: Katowice
country: Poland
facility: NZOZ Centrum Medyczne "Dendryt"
city: Warsaw
country: Poland
facility: Fundacja Epileptologii profesora Jerzego Majkowskiego
city: Warszawa
country: Poland
facility: Instytut Psychaitrii I Neurologii, II Klinika Neurologiczna
city: Bucharest
country: Romania
facility: Roceanu Adina Maria Neurology Individual Medical Center
city: Bucharest
country: Romania
facility: Sapiens Medical Center SRL
city: Belgrade
country: Serbia
facility: Clinical of Neurology, Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Institute of Mental Health
city: Kragujevac
country: Serbia
facility: Clinical Hospital Center Kragujevac
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio - Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Ruber Internacional - Programa Epilepsia
city: Madrid
country: Spain
facility: Fundación Jiminez Diaz-Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos, Serv. Neurologia
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe - Servicio Neurologia
city: Na Muang
country: Thailand
facility: Srinagarind Hospital
state: Khon Kaen
city: Kharkiv
country: Ukraine
facility: 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: Kyiv
country: Ukraine
facility: TDC "Epilepsy" based on Department #19 of Kiev Territorial Medical Association "Psychiatry"
city: Lviv
country: Ukraine
facility: 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: Odessa
country: Ukraine
facility: MI "Odessa Regional Clinical Hospital," Neurological and Neurosurgical Center based on Neurosurgery Department
city: Uzhgorod
country: Ukraine
facility: Department #2 of Regional Clinical Center of Neurosurgery and Neurology
Study officials:
References:
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 Sep 5;99(10):e989-e998. doi: 10.1212/WNL.0000000000200792.
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.
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.
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.