Dose-Optimization, Adjunctive Treatment Study of Ezogabine/Retigabine Immediate Release in Partial-onset Seizures

Inclusion Criteria:

• A male or female of 18 years of age or above capable of giving written informed consent
• Have a confident diagnosis of epilepsy for >=6 months with partial-onset seizures (POS), i.e., simple or complex POS with or without secondary generalization (classified according to the International League Against Epilepsy (ILAE) Guidelines, prior to the Screening Visit
• Currently receiving monotherapy treatment with an antiepileptic drug (AED) at a stable dose for at least 28 days prior to the screening visit (Visit 1). If the subject is taking a barbiturate (e.g., phenobarbital), the dose must be stable for ≥3 months prior to the Screening Visit. Note: Subjects who have received previous adjunctive treatment but are currently taking one AED are eligible for enrolment.
• Investigator-confirmed partial seizure frequency rate of ≥3 partial seizures per 28 days over the 8 weeks preceding the screening visit and must not have been seizure-free for ≥ 21 consecutive days.
• Female of non-child bearing potential, or female of child-bearing potential willing to use protocol-specified methods of contraception to prevent pregnancy during the study.
• Capable to comply with dosing of study drug, background AED, all study procedures and to maintain an accurate and complete daily written Seizure Calendar and Functional Status Diary

Exclusion Criteria:

• Have generalized epilepsy (e.g. Lennox-Gastaut, Juvenile Myoclonic epilepsy, Absence, etc.) or non-epileptic seizures.
• Have had innumerable seizures within the 12-month period prior to the Screening Visit where the individual seizures cannot be counted.
• Have had status epilepticus within 12 months prior to screening
• Have a history of pseudo seizures, non-epileptic events or any other type of psychogenic seizures that could be confused with seizures.
• Have been treated with felbamate or vigabatrin within the 6 months prior to Screening. If a subject has been previously treated with vigabatrin >6 months prior to Screening, a visual perimetry test performed within 6 months prior to Screening must show normal visual fields or no worsening of recognized visual field abnormalities as compared with prior to vigabatrin treatment

• Benzodiazepines used in any manner other than acute usage as defined in this protocol will be considered concurrent AED usage and will not be permitted

  • Are using Central Nervous System (CNS)-active medication (other than concomitant AED therapy), unless the subject has been stabilized on such medication for at least 1 month prior to the Screening Visit.
• Are using herbal treatments with CNS activity within at least 1 month prior to the Screening Visit
• Have received ezogabine/retigabine in a previous study or have taken POTIGA or TROBALT.
• Are currently following or planning to follow the ketogenic diet
• Have an active Vagus Nerve Stimulator (VNS) to control seizures
• Are planning surgery to control seizures during the study
• Have impaired renal function as judged by a creatinine clearance of <50 mL/min
• Have a history of urinary retention or risk factors for urinary retention that in the investigator's judgment could potentially affect subject safety.
• Have an average corrected QT interval (QTc), using Bazett's QT correction (QTcB), ≥450msec or ≥480msec for subjects with bundle branch block at the time of the Screening Visit
• Liver function tests: alanine aminotransferase (ALT) is ≥2 times the upper limit of normal (ULN); alkaline phosphatase and bilirubin are >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%).
• Are suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that are likely to interfere with the objectives of the study
• Have a history of malignancy within the past 2 years; with the exception of basal cell carcinoma
• Have unstable liver disease [chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria; chronic stable Hepatitis B to be excluded if significant immunosuppressive agents administered due to risk of hepatitis B reactivation]
• Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs
• Have an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Have history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
• Have a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to screening
• Have a known hypersensitivity to any components of the study medication
• Have taken an investigational drug, or used an investigational device, within the previous 30 days prior to screening or plans to take an investigational drug anytime during the study.