Clinical trial NCT01721317
Conditions: Seizures
Keywords: Ezogabine/Retigabine Adjunctive Treatment Safety Efficacy Epilepsy Tolerability Immediate Release GW582892 Dose-Optimization Partial-Onset Seizures
Sponsor: GlaxoSmithKline
Start date: 2012-12-19; Completion date: 2013-06-20
Enrollment: 6 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase IV adjunctive treatment dose-optimization study evaluating the efficacy, safety, and health outcomes of ezogabine/retigabine immediate release (IR) (GW582892) compared with placebo in adult subjects with partial-onset seizures (POS). This randomized, double-blind, placebo-controlled, parallel-group, multicenter study will compare ezogabine/retigabine IR (investigator-selected daily doses of 600 milligram (mg)/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day) with placebo. Study drug will be taken three times a day (TID) in equally or unequally divided doses.

The study design includes up to a 10-week (wk) Screening (≤2 wks)/Baseline (8 wks) Phase, a Titration Phase (2 wks), Dose-Optimization Phase (8 wks), Maintenance Phase (8 wks), and Taper/Follow-Up Phase (3 wks). The total duration of the study for each subject will be approximately 31 wks, and at minimum approximately 27 wks if subjects provide reliable 28-day retrospective seizure data.

Approximately 280 subjects will be screened with approximately 208 subjects randomly assigned to 1 of 2 treatment groups in a 2:1 ratio (ezogabine/retigabine IR, or placebo).

Subjects will be instructed to start investigational product (IP) the day after the baseline visit. During the first week of the Titration Phase, subjects will be taking 300 mg/day (100 mg TID). During the second week, subjects will be taking 450 mg/day (150 mg/day TID).

At the beginning of the Dose-Optimization Phase (3rd week of study drug) subjects will take 600 mg/day (200 mg TID) for one week. Thereafter during the Dose-Optimization Phase, subjects will continue to increase their daily dose by 150 mg per week until they have achieved their optimal tolerated dose. During this phase, the investigator may choose to have the subject stay on his/her designated dose for another week before attempting a dose increase until reaching a dose of 1200 mg/day. In addition, in the context of tolerability issues, the subject may be reduced to the preceding dose level for one week before attempting to increase the dose again at the next scheduled time point until the subject reaches optimal dose. Subjects unable to tolerate a minimum of 600 mg/day will be discontinued from the study.

The Maintenance Phase will begin at Week 10 (Visit 8) and will last 8 weeks. During the Maintenance Phase, subjects will remain on the daily TID dose achieved at the end of the Dose-Optimization Phase.

Seizure type and frequency will be monitored throughout the study via a Seizure Calendar and will be evaluated at each study visit. Subjects will be instructed to complete the daily Seizure Calendar during each phase of the study.

Detailed description:

Arms: arm 1: Subjects receive Ezogabine/Retigabine 300 mg equally divided TID over Wk 1 arm 2: Subjects receive matching Placebo arm 3: Subjects receive Ezogabine/Retigabine 450 mg equally divided TID over Wk 2 arm 4: Subjects receive matching Placebo arm 5: 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 arm 6: Subjects receive matching Placebo arm 7: 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 arm 8: Subjects receive matching Placebo arm 9: 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 arm 10: Subjects receive matching Placebo arm 11: 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 arm 12: Subjects receive matching Placebo arm 13: 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 arm 14: Subjects receive matching Placebo arm 15: 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) arm 16: Subjects receive matching Placebo
Interventions: intervention 1: Ezogabine/Retigabine IR intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects received drug (dose strength 300 mg to 1200 mg) orally with or without food. The 3 daily doses are to be administered with approximately an 8-hour interval between them. intervention 2: Matching placebo will be available

Protocol documents: