Dose-Optimization, Adjunctive Treatment Study of Ezogabine/Retigabine Immediate Release in Partial-onset Seizures
Status:
Terminated
Trial end date:
2013-06-20
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
GlaxoSmithKline
Collaborators:
Bausch Health Americas, Inc. Valeant Pharmaceuticals International, Inc.