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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Partial Epilepsy

Intervention / Treatment
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* Drug: YKP3089
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br> <br> |
| Experimental: YKP3089 Low Dose<br>YKP3089 Low Dose | Drug: YKP3089<br> <br> |
| Experimental: YKP3089 Medium Dose<br>YKP3089 Medium Dose | Drug: YKP3089<br> <br> |
| Experimental: YKP3089 High Dose<br>YKP3089 High Dose | Drug: YKP3089<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 50% Responder Rate | Percentage of patients achieving a 50% or more reduction from baseline in partial seizure frequency during the double-blind treatment period | 18 weeks |