Epilepsy MedDRA version: 14.1 Level: PT Classification code 10015037 Term: Epilepsy System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Trobalt®
Product Name: Trobalt
Product Code: GW582892
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW582892
Other d
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult subjects =18 years of age. 2. Have given written informed consent, or has a legally authorized representative who has given written informed consent, prior to the performance of any study assessments. 3. Have a confident diagnosis of epilepsy for =6 months with POS, i.e., simple or complex POS with or without secondary generalization, prior to the Screening Visit. 4. Currently receiving monotherapy treatment with an 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. 5. Have an 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. 6. Are able and willing to maintain an accurate and complete daily written Seizure Calendar and Functional Status Diary at specified time points or has a caregiver who is able and willing to maintain an accurate and complete daily written Seizure Calendar for the entire duration of the study. 7. Are able to comply with dosing of study drug, background AED and all study procedures. 8. A female subject is eligible to enter and participate in the study if she is: a. Of non-childbearing potential • Premenopausal females with a documented (medical report verification) hysterectomy with or without oophorectomy or bilateral oophorectomy when reproductive status has been confirmed by hormone level assessment. • Postmenopausal females defined as being amenorrheic for greater than 1 year with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by estradiol and follicle-stimulating hormone (FSH) levels consistent with menopause (according to local laboratory ranges). Women who have not been confirmed as post-menopausal should be advised to use contraception as outlined in Appendix 1 of the study protocol. b. Of child-bearing potential, has a negative pregnancy test at Screening and Randomization (Week 0), and agrees to satisfy one of the requirements as listed in Appendix 1of the study protocol. c. Not pregnant (confirmed by pregnancy test) or lactating (breastfeeding) or planning to become pregnant during the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 198 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Have generalized epilepsy (e.g. Lennox-Gastaut, Juvenile Myoclonic epilepsy, Absence, etc.) or non-epileptic seizures. 2. Have had innumerable seizures within the 12-month period prior to the Screening Visit where the individual seizures cannot be counted. 3. Have had status epilepticus within 12 months prior to screening. 4. Have a history of pseudo seizures, non-epileptic events or any other type of psychogenic seizures that could be confused with seizures. 5. 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. 6. 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. 7. Are using 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. 8. Are using herbal treatments with CNS activity within at least 1 month prior to the Screening Visit. 9. Have received ezogabine/retigabine in a previous study or have taken POTIGA or TROBALT™. 10. Are currently following or planning to follow the ketogenic diet. 11. Have an active Vagus Nerve Stimulator (VNS) to control seizures. 12. Are planning surgery to control seizures during the study. 13. Have impaired renal function as judged by a creatinine clearance of 1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%). 17. 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. 18. Have a history of malignancy within the past 2 years; with the exception of basal cell carcinoma. 19. 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]. 20. Have any medical condition that, in the investigator’s judgement, 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. 21. 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. 22. Have a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of ezogabine/retigabine IR as an adjunctive treatment for POS in adults with epilepsy who have inadequate control of their seizures with a single AED.;Secondary Objective: • To evaluate individualized dose selection or adjustment on the basis of tolerability and efficacy in a manner intended to simulate clinical practice. • To evaluate the safety and tolerability of ezogabine/retigabine IR as an adjunctive treatment for POS in adults with epilepsy. • To evaluate efficacy and safety in population subsets categorized by the primary mechanism of action of the background AED to which ezogabine/retigabine IR is added (sodium channel blockers or non-sodium channel blockers). • To evaluate the effect of ezogabine/retigabine IR as adjunctive treatment on functional status (worry, activity limitations) and productivity.;Primary end point(s): The primary efficacy endpoint is the percent change in 28-day total partial-onset seizure frequency from the Baseline Phase to the Double-Blind Phase (Titration Phase, Dose-Optimization Phase and Maintenance Phase) in subjects randomly assigned to ezogabine/retigabine IR compared with placebo.;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint analysis will be based on data collected from subject-completed Seizure Calendars. Subjects’ daily-completed seizure calendars will be reviewed and collected at clinic visits. Following Visit 3 (baseline) subjects will attend a clinic visit every two weeks for 10 weeks, and then every 4 weeks for 8 weeks, and then a follow-up visit after 3 weeks of drug taper. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percent change in total partial seizure frequency per 28 days, for the following intervals: Maintenance Phase, Dose-Optimization + Maintenance Phase • Proportion of responders experiencing a =50% reduction from baseline to the end of the period, in total partial seizure frequency per 28 days, for the following intervals: Double-Blind period, Maintenance Phase, Dose-Optimization + Maintenance Phase • Proportion of seizure free subjects for the following intervals: Maintenance Phase, and the Dose-Optimization + Maintenance Phase • Change from baseline in the number of seizure free days for the following intervals: Double-Blind period, Maintenance Phase, and the Dose-Optimization + Maintenance Phase. ;Timepoint(s) of evaluation of this end point: The secondary efficacy endpoints analyses will be based on data collected from subject-completed Seizure Calendars. Subjects’ daily-completed seizure calendars will be reviewed and collected at clinic visits. Following Visit 3 (baseline) subjects will attend a clinic visit every two weeks for 10 weeks, and then every 4 weeks for 8 weeks, and then a follow-up visit after 3 weeks of drug taper. | — |
Countries
Greece, United States
Contacts
Public ContactGSK Clinical Support HelpDesk
GlaxoSmithKline Research & Development Limited
Outcome results
None listed