Dose-Optimization, Adjunctive Treatment Study of Ezogabine/Retigabine Immediate Release in Partial-onset Seizures
Seizures
About this trial
This is an interventional treatment trial for Seizures focused on measuring Ezogabine/Retigabine, Adjunctive Treatment, Safety, Efficacy, Epilepsy, Tolerability, Immediate Release, GW582892, Dose-Optimization, Partial-Onset Seizures
Eligibility Criteria
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Arm 16
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Titration Phase: Ezogabine/Retigabine 300 mg
Titration Phase: Placebo 300 mg
Titration Phase: Ezogabine/Retigabine 450 mg
Titration Phase: Placebo 450 mg
Dose-Optimization Phase: Ezogabine/Retigabine 600 mg
Dose-Optimization Phase: Placebo 600 mg
Dose-Optimization Phase: Ezogabine/Retigabine 750 mg
Dose-Optimization Phase: Placebo 750 mg
Dose-Optimization Phase: Ezogabine/Retigabine 900 mg
Dose-Optimization Phase: Placebo 900 mg
Dose-Optimization Phase: Ezogabine/Retigabine 1050 mg
Dose-Optimization Phase: Placebo 1050 mg
Dose-Optimization Phase: Ezogabine/Retigabine 1200 mg
Dose-Optimization Phase: Placebo 1200 mg
Maintenance Phase:Ezogabine/Retigabine
Maintenance Phase: Placebo
Subjects receive Ezogabine/Retigabine 300 mg equally divided TID over Wk 1
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine 450 mg equally divided TID over Wk 2
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine 600 mg equally divided (200 mg TID) over Wk 3 or until they achieve their optimal tolerated dose as assessed by the Investigator
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine 750 mg equally or unequally divided TID over Wk 4 or until they achieve their optimal tolerated dose as assessed by the Investigator
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine 900 mg equally or unequally divided TID over Wk 5 or until they achieve their optimal tolerated dose as assessed by the Investigator
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine 1050 mg equally or unequally divided TID over Wk 6 or until they achieve their optimal tolerated dose as assessed by the Investigator
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine 1200 mg equally divided (400 mg TID) over Wk 7 or until they achieve their optimal tolerated dose as assessed by the Investigator
Subjects receive matching Placebo
Subjects receive Ezogabine/Retigabine at the daily dose achieved (equally or unequally divided TID) at the end of the Dose-Optimization Phase for 8 Weeks (600 mg, 750 mg, 900 mg, 1050 mg, or 1200 mg)
Subjects receive matching Placebo