A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures

NCT01866111 | Completed Phase 2 Results DMC

• 1 other identifier: YKP3089C017
• Study Type: interventional
• Target: 437
• Locations: 15 countries
• Sites: 67

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.

Conditions

Partial Epilepsy

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline and 18 weeks

Secondary Outcomes (1)

• 50% Responder Rate

  18 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

YKP3089 Low Dose

EXPERIMENTAL

YKP3089 Low Dose

Drug: YKP3089

YKP3089 Medium Dose

EXPERIMENTAL

YKP3089 Medium Dose

Drug: YKP3089

YKP3089 High Dose

EXPERIMENTAL

YKP3089 High Dose

Drug: YKP3089

Interventions

YKP3089 DRUG

YKP3089 High Dose; YKP3089 Low Dose; YKP3089 Medium Dose

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (67)

St. Joseph's Hospital and Medical Center - Barrow Neurology Clinics

Phoenix, Arizona, 85013, United States

Location

Clinical Trials, Inc.

Little Rock, Arkansas, 72205, United States

Location

Kaiser Permanente, Department of Neurology

Anaheim, California, 92806, United States

Location

Neuro-Pain Medical Center

Fresno, California, 93710, United States

Location

West Los Angeles VA Medical Center, Clinical Research Center

Los Angeles, California, 90073, United States

Location

Neuroresearch, Inc. - Torrance

Torrance, California, 90505, United States

Location

Neuroresearch II, Inc.

Ventura, California, 93003, United States

Location

Bradenton Research Center, Inc.

Bradenton, Florida, 34205, United States

Location

Lovelace Scientific Resources, Inc.

Sarasota, Florida, 34233, United States

Location

Consultants in Epilepsy & Neurology, PLLC

Boise, Idaho, 83702, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Neurology Clinic PC

Waldorf, Maryland, 20603, United States

Location

The Comprehensive Epilepsy Care Center for Children and Adults

St Louis, Missouri, 63017, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

NYU Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

The Neurological Institute, PA

Charlotte, North Carolina, 28204, United States

Location

Thomas Jefferson Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt Epilepsy Clinic

Nashville, Tennessee, 37232, United States

Location

Austin Epilepsy Care Center

Austin, Texas, 78758, United States

Location

University of Virginia Comprehensive Epilepsy Program

Charlottesville, Virginia, 22903, United States

Location

Institute of Neurological Sciences, Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St. Vincent's Hospital (Melbourne)

Fitzroy, Victoria, 3065, Australia

Location

Epilepsy Research Centre, Melbourne Brain Centre

Heidelberg, Victoria, 3084, Australia

Location

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

University Multiprofile Hpspital for Active Treatment "Sveti Georgi" EAD, Clinic of Neurological Diseases

Plovdiv, 4002, Bulgaria

Location

"First Multiprofile Hospital for Active Treatment - Sofia" EAD, Neurology Clinic

Sofia, 1142, Bulgaria

Location

University of Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD, Clinic of Neurological Diseases

Sofia, 1606, Bulgaria

Location

Fakultní nemocnice Ostrava, Neurologická klinika

Ostrava, 70825, Czechia

Location

Mediscan Group, s.r.o

Prague, 148 00, Czechia

Location

Fakultni nemocnice v Motole, Neurologická klinika

Prague, 150 06, Czechia

Location

CHU - Service Neurophysiologie Clinique

Dijon, 21079, France

Location

Hôpital Central - CHU de Nancy - Service de Neurologie

Nancy, 5400, France

Location

Epilepsiezentrum Berlin- Bradenburg, Epilepsieklinik "Tabor"

Bernau bei Berlin, 16321, Germany

Location

Krankenhaus Mara gGmbH, Epilepsiezentrum Bethel

Bielefeld, 33617, Germany

Location

Epilepsiezentrum Kork

Kehl, 77694, Germany

Location

Országos Klinikai Idegtudományi Intézet

Budapest, 1145, Hungary

Location

Department of Neurology, Hadassah University Hospital Ein Kerem, Kiryat Hadassah

Jerusalem, 91120, Israel

Location

Western Galilee Hospital, Department of Neurology

Nahariya, 22100, Israel

Location

The Chaim Sheba Medical Center, Department of Neurology

Ramat Gan, 52621, Israel

Location

M.A. - LEK A.M. Maciejowscy S.C. Centrum Terapii SM

Katowice, 40-595, Poland

Location

NOVO-MED Zielinski I Wspolnicy Spolka Jawna

Katowice, 40-650, Poland

Location

NZOZ Centrum Medyczne "Dendryt"

Katowice, 40-662, Poland

Location

Fundacja Epileptologii profesora Jerzego Majkowskiego

Warsaw, 02-952, Poland

Location

Instytut Psychaitrii I Neurologii, II Klinika Neurologiczna

Warsaw, 02-957, Poland

Location

Roceanu Adina Maria Neurology Individual Medical Center

Bucharest, 010042, Romania

Location

Sapiens Medical Center SRL

Bucharest, 011635, Romania

Location

Clinical of Neurology, Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Institute of Mental Health

Belgrade, 11000, Serbia

Location

Clinical Hospital Center Kragujevac

Kragujevac, 34000, Serbia

Location

Dong-A University Hospital

Busan, 602715, South Korea

Location

Seoul National University Hospital

Seoul, 110744, South Korea

Location

Samsung Medical Center

Seoul, 135710, South Korea

Location

Asan Medical Center

Seoul, 138736, South Korea

Location

Konkuk University Medical Center

Seoul, 143729, South Korea

Location

Hospital Universitario San Cecilio - Servicio de Neurologia

Granada, 18012, Spain

Location

Hospital Ruber Internacional - Programa Epilepsia

Madrid, 28034, Spain

Location

Fundación Jiminez Diaz-Servicio de Neurologia

Madrid, 28040, Spain

Location

Hospital Clinico Universitario San Carlos, Serv. Neurologia

Madrid, 28040, Spain

Location

Hospital Universitario y Politecnico La Fe - Servicio Neurologia

Valencia, 46026, Spain

Location

Srinagarind Hospital

Na Muang, Changwat Khon Kaen, 40002, Thailand

Location

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"

Kharkiv, 61103, Ukraine

Location

TDC "Epilepsy" based on Department #19 of Kiev Territorial Medical Association "Psychiatry"

Kyiv, 04080, Ukraine

Location

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

Lviv, 79010, Ukraine

Location

MI "Odessa Regional Clinical Hospital," Neurological and Neurosurgical Center based on Neurosurgery Department

Odesa, 65025, Ukraine

Location

Department #2 of Regional Clinical Center of Neurosurgery and Neurology

Uzhhorod, 88018, Ukraine

Location

Related Publications (4)

• 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.

  PMID: 35705501 DERIVED

• 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.

  PMID: 33662894 DERIVED

• 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.

  PMID: 31734103 DERIVED

• 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.

  PMID: 25769377 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: Chief Medical Officer
• Organization: SK Life Science

mkamin@sklsi.com

201-421-3830

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: May 31, 2013
• Study Start: July 31, 2013
• Primary Completion: April 5, 2021
• Study Completion: October 31, 2021
• Last Updated: June 24, 2025
• Results First Posted: April 29, 2022

Record last verified: 2025-06

Locations

RO (2); KR (5); AU (5); UA (5); IL (3); ES (5); HU (1); PL (5); SE (3); DE (3); BU (3); TH (1); US (21); FR (2); CZ (3)