Clinical trial NCT01648101
Conditions: Epilepsy
Keywords: Retigabine IR Asian Subjects Adjunctive Therapy Efficacy Drug-Resistant Safety & tolerability Partial-Onset Seizures Epilepsy
Sponsor: GlaxoSmithKline
Start date: 2012-08-29; Completion date: 2013-12-23
Enrollment: 76 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The immediate release (IR) formulation of retigabine has been shown to be superior to placebo as adjunctive therapy in 3 adequate and well-controlled studies in subjects with drug-resistant partial-onset seizures (POS) who had previously failed to respond to two or more antiepileptic drugs (AEDs) and were still having seizures despite current treatment with 1, 2, or 3 AEDs. However, of 1244 subjects randomly assigned to treatment in these 3 clinical studies, only 10 were Asian subjects and only 5 of these Asian subjects were randomly assigned to treatment with retigabine. Therefore, this Phase III study is being conducted to evaluate the efficacy, safety and tolerability, and health outcomes of retigabine, at doses of 900 mg/day and 600 mg/day, compared with placebo in adult Asian subjects with drug-resistant POS.

Detailed description:
This is a Phase III study evaluating the efficacy, safety and tolerability, and health outcomes of 2 doses of retigabine immediate release (IR) (GW582892) compared with placebo in adult Asian subjects with drug-resistant partial-onset seizures (POS) who are already taking 1, 2, or 3 antiepileptic drugs (AEDs). This randomised, double-blind, placebo-controlled, parallel-group study will compare retigabine IR at doses of 900 mg/day and 600 mg/day taken in equally divided doses three times a day with placebo.

The study design includes an 8-week Screening/Baseline Phase, a 16-week Treatment Phase (4-week Titration Phase and 12-week Maintenance Phase), and a 4-week Transition or Taper/Follow-up Phase. Approximately 500 subjects will be screened and enrolled with approximately 354 subjects randomly assigned to 1 of 3 treatment groups in a ratio of 1:1:1 (retigabine 900 mg/day, retigabine 600 mg/day, or placebo). The total duration of the study for each subject will be approximately 28 weeks. At the end of the Maintenance Phase, eligible subjects will be given the opportunity to enrol in an open-label extension study.

The primary efficacy endpoint is the proportion of responders, defined as subjects with \>/=50% reduction in 28 day total POS frequency, from the Baseline Phase to the Maintenance Phase, in subjects randomly assigned to retigabine 900 mg/day compared with placebo. The key secondary efficacy endpoint is the proportion of responders, defined as subjects with \>/=50% reduction in 28 day total POS frequency, from the Baseline Phase to the Maintenance Phase, in subjects randomly assigned to retigabine 600 mg/day compared with placebo.

The safety and tolerability endpoints are incidence and severity of adverse events (AEs); proportion of subjects with AEs leading to discontinuation; change from Baseline in vital sign measurements and weight; change from Baseline in electrocardiogram parameters; change from Baseline in haematology, chemistry, and urinalysis parameters; changes from Baseline in American Urological Association Symptom Index and post-void residual bladder ultrasound volumes; and summary of the Columbia-Suicide Severity Rating Scale.

Arms: arm 1: 900mg total daily dose arm 2: 600mg total daily dose arm 3: Placebo
Interventions: intervention 1: Retigabine 900mg/day intervention 2: Retigabine 600mg/day intervention 3: Placebo
Intervention descriptions: intervention 1: Study drug will be administered three times a day in a double blind manner. The starting dose of retigabine will be 300 mg/day. This dose will be increased by 150 mg/day per week to reach the target dose of 900mg/day over a 4 week Titration Phase). The subject will then continue to receive 900mg/day for the next 12 weeks (Maintenance Phase). Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. After a 4 week transition phase, eligible subjects will start the OLE on retigabine 900mg/day. intervention 2: Study drug will be administered three times a day in a double blind manner. The starting dose of retigabine will be 300mg/day. This dose will be increased by 150 mg/day per week to reach the target dose of 600mg/day over 2 weeks. The subject will then continue to receive 600mg/day for the next 14 weeks (2 weeks of the Titration Phase and 12 weeks of the Maintenance Phase). Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. After a 4 week Transition Phase (3 weeks on retigabine 600mg/day, 1 week on retigabine 750mg/day) eligible subjects will start the OLE on retigabine 900mg/day. intervention 3: Study drug will be administered three times a day in a double blind manner. Subjects randomised to placebo will receive the same number, size and colour of tablets as the 600mg/day and 900mg/day treatment arms for the duration of the 4 week Titration Phase and the 12 week Maintenance Phase. Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. The starting dose of retigabine will be 300 mg/day. This dose will be increased by 150 mg/day per week to reach dose of 750mg/day over the 4 weeks of the Transition Phase. On completion of the Transition Phase eligible subjects will start the OLE on retigabine 900mg/day.

Protocol documents: