Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
This is a multicenter, open label study to assess the safety and pharmacokinetics of YKP3089
 as adjunctive therapy in subjects with partial onset seizures. Initially, subjects taking
 phenytoin or phenobarbital will be enrolled followed by additional subjects taking
 anti-epileptic drugs other than phenytoin and phenobarbital to further investigate long-term
 safety.
see above
Inclusion Criteria

 1. Male or female and greater than or equal to 18 years of age at the time of signing the
 informed consent. The upper age limit is 70 years inclusive.

 2. Weight at least 30 kg

 3. Written informed consent signed by the subject or legal guardian prior to entering the
 study in accordance with the ICH GCP guidelines. If the written informed consent is
 provided by the legal guardian because the subject is unable to do so, a written or
 verbal assent from the subject must also be obtained. In Germany, only the subject may
 sign the informed consent form in accordance with ICH guidelines.

 4. 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).

 5. Have uncontrolled partial seizures and require additional AED therapy despite having
 been treated with at least one AED within approximately the last 2 years.

 6. Currently on stable antiepileptic treatment regimen:

 1. Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks
 prior to Visit 2

 2. Vagal nerve stimulator (VNS) will not be counted as an AED; however, the
 parameters must remain stable for at least 4 weeks prior to baseline. The VNS
 must have been implanted at least 5 months prior to Visit 1.

 3. Benzodiazepines taken at least once per week during the 1 month prior to Visit 1
 for epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED and must
 be continued unchanged throughout the study. Therefore only a maximum of 2
 additional approved AEDs will be allowed.

 7. Computed tomography (CT) or magnetic resonance imaging (MRI) scan performed within the
 past 10 years that ruled out a progressive cause of epilepsy. If a CT or MRI has not
 been performed within the past 10 years, one must be performed prior to randomization.

 8. Ability to reach subject by telephone.

 9. Use of an acceptable form of birth control by female subjects of childbearing
 potential

 Exclusion Criteria

 1. History of any serious drug-induced hypersensitivity reaction (including but not
 limited to Stevens Johnson syndrome, toxic epidermal necrolysis, drug reaction with
 eosinophilia and systemic symptoms) or any drug-related rash requiring
 hospitalization.

 2. History of any drug-induced rash or hypersensitivity reaction.

 3. History of a first degree relative with a serious cutaneous drug-induced adverse
 reaction.

 4. History of serious systemic disease, including hepatic insufficiency, renal
 insufficiency, a malignant neoplasm, any disorder in which prognosis for survival is
 less than 3 months, or any disorder which in the judgment of the investigator will
 place the subject at excessive risk by participation in a controlled trial

 5. Subjects taking phenytoin must not be taking phenobarbital or primidone; subjects
 taking phenobarbital must not be taking phenytoin or primidone

 6. Subjects taking concomitant AEDs other than phenytoin or phenobarbital, must not be
 taking phenytoin or phenobarbital or primidone

 7. Subjects with clinical evidence of phenytoin or phenobarbital toxicity

 8. A history of nonepileptic or psychogenic seizures

 9. Presence of only nonmotor simple partial seizures or primary generalized epilepsies

 10. Presence of Lennox-Gastaut syndrome

 11. Scheduled epilepsy surgery within 8 months after Visit 1

 12. Subjects implanted with or planning to have implantation of deep brain stimulator

 13. Pregnancy or lactation

 14. Any clinically significant laboratory abnormality that in the opinion of the
 investigator would exclude the subject from the study

 15. Evidence of significant active hepatic disease. Stable elevations of liver enzymes,
 alanine aminotransferase (ALT), and aspartate aminotransferase (AST) due to
 concomitant medication(s) will be allowed if they are less than 3 times the upper
 limit of normal (ULN)

 16. 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

 17. 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

 18. Presence of psychotic disorders and/or unstable recurrent affective disorders evident
 by use of antipsychotics; presence or recent history (within 6 months) of major
 depressive episode

 19. History of alcoholism, drug abuse, or drug addiction within the past 2 years

 20. Current use of felbamate with less than 18 months of continuous exposure

 21. Current or recent (within the past year) use of vigabatrin or ezogabine. Subjects with
 a prior history of treatment with vigabatrin must have documentation showing no
 evidence of a vigabatrin associated clinically significant abnormality in a visual
 perimetry test. Subjects with a prior history of treatment with ezogabine should have
 no evidence of retinal abnormalities with funduscopic features similar to those seen
 in retinal pigment dystrophies.

 22. History of status epilepticus within 3 months of Visit 1

 23. Screening laboratory investigation demonstrates abnormal renal function

 24. Absolute neutrophil count less than 1500/µL

 25. Clinical or ECG evidence of serious cardiac disease, including ischemic heart disease,
 uncontrolled heart failure, and major arrhythmias, or relevant replicated changes in
 QT intervals (QTcF less than 340 msec or greater than 450 msec in males and greater
 than 470 msec in females)

 26. Platelet counts lower than 80,000/µL in subjects treated with VPA

 27. 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.

 28. More than 1 lifetime suicide attempt

 29. Participation in any other trials involving an investigational product or device
 within 30 days of screening (or longer, as required by local regulations)

 30. Current use of any of the following medications: clopidogrel, fluvoxamine,
 amitriptyline, clomipramine, bupropion, methadone, ifosfamide, cyclophosphamide,
 efavirenz, fosphenytoin, ethotoin, mephenytoin, or natural progesterone (within 1
 month of Visit 1)

 31. History of positive antibody/antigen test for hepatitis B, hepatitis C, or HIV

 32. Presence of congenital short QT syndrome

 33. A history of previous exposure to YKP3089