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

• ClinicalTrials.gov Identifier: NCT01866111
• Recruitment Status: Completed
• First Posted: May 31, 2013
• Results First Posted: April 29, 2022
• Last Update Posted: April 29, 2022
• Sponsor: SK Life Science, Inc.
• Information provided by (Responsible Party): SK Life Science, Inc.

Tracking Information

• First Submitted Date: May 28, 2013
• First Posted Date: May 31, 2013
• Results First Submitted Date: August 20, 2020
• Results First Posted Date: April 29, 2022
• Last Update Posted Date: April 29, 2022
• Actual Study Start Date: July 31, 2013
• Actual Primary Completion Date: April 5, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 4, 2022)

Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days [ Time Frame: baseline and 18 weeks ]

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.

• Original Primary Outcome Measures (submitted: May 28, 2013): Percent reduction in seizure frequency (average 28-day seizure rate) of complex partial and/or secondarily generalized and/or simple partial motor seizures during the double-blind phase relative to the pretreatment baseline. [ Time Frame: 18 weeks ]

Current Secondary Outcome Measures (submitted: April 4, 2022)

50% Responder Rate [ Time Frame: 18 weeks ]

Percentage of patients achieving a 50% or more reduction from baseline in partial seizure frequency during the double-blind treatment period

• Original Secondary Outcome Measures (submitted: May 28, 2013): The response to treatment, defined as a 50% or greater reduction during the double blind phase in the seizure frequency from baseline for the ITT subjects. [ Time Frame: 18 weeks ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Partial Epilepsy

Intervention

• Drug: YKP3089
• Drug: Placebo

Study Arms

• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo
• Experimental: YKP3089 Low Dose
  YKP3089 Low Dose
  Intervention: Drug: YKP3089
• Experimental: YKP3089 Medium Dose
  YKP3089 Medium Dose
  Intervention: Drug: YKP3089
• Experimental: YKP3089 High Dose
  YKP3089 High Dose
  Intervention: Drug: YKP3089

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 21, 2015): 437
• Original Estimated Enrollment (submitted: May 28, 2013): 400
• Actual Study Completion Date: October 31, 2021
• Actual Primary Completion Date: April 5, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Bulgaria, Czechia, France, Germany, Hungary, Israel, Korea, Republic of, Poland, Romania, Serbia, Spain, Thailand, Ukraine, United States
• Removed Location Countries: Czech Republic, United Kingdom

Administrative Information

• NCT Number: NCT01866111
• Other Study ID Numbers: YKP3089C017
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: SK Life Science, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: SK Life Science, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: SK Life Science, Inc.
• Verification Date: April 2022