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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01866111




Registration number
NCT01866111
Ethics application status
Date submitted
28/05/2013
Date registered
31/05/2013
Date last updated
29/04/2022

Titles & IDs
Public title
A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
Scientific 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
Secondary ID [1] 0 0
YKP3089C017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Partial Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Placebo comparator: Placebo - Placebo

Experimental: YKP3089 Low Dose - YKP3089 Low Dose

Experimental: YKP3089 Medium Dose - YKP3089 Medium Dose

Experimental: YKP3089 High Dose - YKP3089 High Dose
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
Timepoint [1] 0 0
baseline and 18 weeks
Secondary outcome [1] 0 0
50% Responder Rate
Timepoint [1] 0 0
18 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/10/2021
Sample size
Target
Accrual to date
Final
437
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Institute of Neurological Sciences, Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
St. Vincent's Hospital (Melbourne) - Fitzroy
Recruitment hospital [4] 0 0
Epilepsy Research Centre, Melbourne Brain Centre - Heidelberg
Recruitment hospital [5] 0 0
The Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
Arkansas
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United States of America
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California
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United States of America
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Florida
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United States of America
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Idaho
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United States of America
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Maryland
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United States of America
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Missouri
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
State/province [14] 0 0
Virginia
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Bulgaria
State/province [15] 0 0
Plovdiv
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
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Czechia
State/province [17] 0 0
Ostrava
Country [18] 0 0
Czechia
State/province [18] 0 0
Praha 4
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Czechia
State/province [19] 0 0
Praha 5
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France
State/province [20] 0 0
Dijon Cedex
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France
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Nancy
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Germany
State/province [22] 0 0
Bernau bei Berlin
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Germany
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Bielefeld
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Germany
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Kehl
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Hungary
State/province [25] 0 0
Budapest
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Israel
State/province [26] 0 0
Jerusalem
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Israel
State/province [27] 0 0
Nahariya
Country [28] 0 0
Israel
State/province [28] 0 0
Ramat-Gan
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Busan
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
Poland
State/province [31] 0 0
Katowice
Country [32] 0 0
Poland
State/province [32] 0 0
Warsaw
Country [33] 0 0
Poland
State/province [33] 0 0
Warszawa
Country [34] 0 0
Romania
State/province [34] 0 0
Bucharest
Country [35] 0 0
Serbia
State/province [35] 0 0
Belgrade
Country [36] 0 0
Serbia
State/province [36] 0 0
Kragujevac
Country [37] 0 0
Spain
State/province [37] 0 0
Granada
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Valencia
Country [40] 0 0
Thailand
State/province [40] 0 0
Khon Kaen
Country [41] 0 0
Ukraine
State/province [41] 0 0
Kharkiv
Country [42] 0 0
Ukraine
State/province [42] 0 0
Kyiv
Country [43] 0 0
Ukraine
State/province [43] 0 0
Lviv
Country [44] 0 0
Ukraine
State/province [44] 0 0
Odessa
Country [45] 0 0
Ukraine
State/province [45] 0 0
Uzhgorod

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
SK Life Science, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01866111
Trial related presentations / 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 Sep 5;99(10):e989-e998. doi: 10.1212/WNL.0000000000200792.
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. doi: 10.1016/S1474-4422(20)30038-7.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01866111