Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures

Inclusion Criteria

• 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.
• Weight at least 30 kg
• Written informed consent signed by the subject or legal guardian prior to entering the study in accordance with the International Conference on Harmonization Good Clinical Practices (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.
• 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 and require additional AED therapy despite having been treated with at least one AED within approximately the last 2 years.
• Currently on stable antiepileptic treatment regimen:
• Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks prior to Visit 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.
• 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.
• 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.
• Ability to reach subject by telephone.
• Use of an acceptable form of birth control by female subjects of childbearing potential

Exclusion Criteria

• 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.
• History of any drug-induced rash or hypersensitivity reaction.
• History of a first degree relative with a serious cutaneous drug-induced adverse reaction.
• 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
• Subjects taking phenytoin must not be taking phenobarbital or primidone; subjects taking phenobarbital must not be taking phenytoin or primidone
• Subjects taking concomitant AEDs other than phenytoin or phenobarbital, must not be taking phenytoin or phenobarbital or primidone
• Subjects with clinical evidence of phenytoin or phenobarbital toxicity
• A history of nonepileptic or psychogenic seizures
• Presence of only nonmotor simple partial seizures or primary generalized epilepsies
• Presence of Lennox-Gastaut syndrome
• Scheduled epilepsy surgery within 8 months after Visit 1
• Subjects implanted with or planning to have implantation of deep brain stimulator
• Pregnancy or lactation
• Any clinically significant laboratory abnormality that in the opinion of the investigator would exclude the subject from the study
• Evidence of significant active hepatic disease. Stable elevations of liver enzymes, alanine aminotra