Refractory Epilepsy Patients with Partial-Onset Seizures
Conditions
Interventions
Product Name: Retigabine 50mg
Product Code: D-23129
GKE-841
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Retigabine
CAS Number: 150812-12-7
Current Sponsor code: D-23129
GKE-841
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film
GKE-841
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Fil
Sponsors
Valeant Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient is male or female, aged 18 to 75 years, inclusive. 2. Patient has a diagnosis of refractory epilepsy with simple partial or complex partial seizures with or without secondary generalization (International League Against Epilepsy [ILAE] classification). Refractory epilepsy is defined by diagnosis of epilepsy for 2 years or longer, and having partial seizures despite having been treated in the past with at least 2 approved AEDs either alone or together at adequate doses for sufficient length of time in the opinion of the investigator. 3. Patient has had, within the last 10 years, one electroencephalogram (EEG) or video EEG and one brain magnetic resonance imaging (MRI) or computerized tomography (CT) with results consistent with diagnosis of partial-onset seizures. If diagnostic studies are negative and if history during clinical assessment suggest a diagnosis of partial-onset seizures, and other diseases have been excluded, the patient can be enrolled. 4. Patient has documented 28-day partial seizure frequency rate of = 4 partial seizures over the 8 weeks preceding the screening visit as calculated by: Total number of partial seizures reported during the evaluation period X 28 days/ Total number of days of available seizure data. Patients should not be seizure free for more than 21 consecutive days. In patients with simple partial seizures, only seizures with motor signs will be counted towards meeting the inclusion criteria. 5. Patient must be currently treated with 1, 2 or 3 established AEDs at a stable dose for at least 1 month before the Screening evaluation. Patients receiving additional treatment with a VNS may be included as long as the VNS has been in place for at least 6 months prior to entry into the study and stimulation parameters have been kept constant for 1 month prior to study enrollment. 6. Women of childbearing potential must be using a medically acceptable method of birth control and have a negative serum ß-human chorionic growth hormone (ß-HCG) pregnancy test from a sample collected at the initial screening visit. A woman of childbearing potential is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months, surgical sterilization, or adequate barrier methods (e.g., diaphragm and foam). Oral contraception alone is not considered adequate for the purpose of this study. Use of oral contraceptives in combination with another method (e.g., a spermicidal cream) would be acceptable. 7. In the opinion of the investigator, patient will be able to understand verbal and written instructions and be competent to comply with all study requirements. 8. Patient or legal guardian (if applicable) is informed, given ample time and opportunity to read and/or understand about his/her participation in the study, and has signed and dated the written informed consent form. * Additional Inclusion Criterion for Randomization The following additional inclusion criterion must also be met at the time of randomization (Visit 3): Patient has documented 28-day partial seizure frequency rate of =4 partial seizures over the 8-week baseline phase as calculated by: Total number of partial seizures reported during the evaluation period X 28 day
Exclusion criteria
Exclusion criteria: 1. Patient has any medical or psychiatric condition, which in the opinion of the investigator could either affect patient’s health by participating in the study or could compromise his/her ability to participate in this study. 2. Patient has clinically significant abnormalities on physical examination, vital signs, ECG, or laboratory tests (>3 x upper limit of normal [ULN]) for ALT, AST, and other LFTs; acute infectious illness within (e. g. UTI, URI) within 7 days of the Screening visit. 3. Patient has impaired renal function as judged by creatinine clearance of <50 mL/min. 4. Patient has QTc interval (Bazett’s) longer than 430 msec for men and 450 msec for women on single ECG at Screening. 5. Patient has history of alcohol or drug abuse within the past 1 year. 6. Patient has evidence of a progressive central nervous system (CNS) disease (e. g. CNS lupus, tumors, multiple sclerosis, Alzheimer's), lesion, or encephalopathy. 7. Patient has history of malignancy within the past 2 years; with an exception of basal cell carcinoma. 8. Patient is pregnant or breastfeeding. 9. Patient has participated in any trial of any investigational drug or device within 2 months of screening visit. 10. Patient has received retigabine in a previous study. 11. Patient has been treated with felbamate or vigabatrin in the previous 6 months; if a patient has previously been treated with vigabatrin, a visual perimetry test prior to screening (or within the past 6 months) must show normal visual fields or no worsening of recognized visual field abnormalities prior to vigabatrin treatment. 12. Patient has history of pseudo seizures, non-epileptic events or any other type of psychogenic seizures which could be confused with seizures. 13. Patient has history of primary generalized seizures. 14. Patient has history of clustering or flurries within the 12-month period preceding study entry where the individual seizures cannot be counted. 15. Patient has history of status epilepticus (both convulsive and non-convulsive status) within the 12-month period preceding study entry. 16. Patient has any condition that would prevent compliance with the study procedures or proper reporting of AEs. 17. In the opinion of the investigator, patient is unable to complete the study. 18. Patient has known hypersensitivity to any components of the investigational product. * Additional Exclusion Criteria for Randomization The following additional exclusion criteria will preclude participation in the study if met at the time of randomization (Visit 3): 1. Patient has had uncountable seizures due to clustering or flurries or an episode of status epilepticus during the 8-week baseline phase (clustering is defined as an episode of seizure activity lasting less than 30 minutes during which several seizures occur with such frequency that the initiation and termination of each individual seizure cannot be distinguished). 2. Patient has an average QTc (Bazett’s) interval longer than 430 msec for men and 450 msec for women on the 3 ECGs carried out at the time of randomization (Visit 3). For any such patients, the QTc reading will be confirmed by t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate a superior change in total partial seizure frequency per 4 weeks from baseline to the double-blind period in patients treated with retigabine dosed at 900 mg/day, in 3 equally divided doses, compared to placebo. ; Secondary Objective: Safety and tolerability To explore the change in total partial seizure frequency per 4 wks from baseline and the proportion of the responders experiencing a =50% reduction in total partial seizure frequency in subjects treated with retigabine dosed at 600 mg/day, in 3 equally divided doses, compared to placebo To demostrate imporvements compared to placebo in: Proportion of the responders experiencing a =50% reduction in total partial seizure frequency per 4wks from basel. to the d-blind period Change in total partial seizure frequency Proportion of patients achieving favorable change in seizure frequency categories Clinical Global Impressions /Patient Global Impressions assessments To compare quality of life/ To collect health economics data To evaluate the steady-state pharmacokinetics of retigabine and other antiepileptic drugs/To investigate the correlation between steady-state plasma concentrations of retigabine and changes in QTc interval. ;Primary end point(s): Reduction of total partial seizure frequency | — |
Countries
Belgium, Germany, Hungary, Spain, United Kingdom
Outcome results
None listed