Retigabine Reduces Seizures In Adults With Inadequately Controlled Partial-Onset Epilepsy
Results from RESTORE 2, a placebo-controlled, Phase III study demonstrated that the investigational compound retigabine significantly reduced the number of seizures in adult patients with refractory partial-onset epilepsy when a 600 mg or 900 mg dose was added to a patient's current anti-epileptic drug (AED) therapy. Prior to enrollment in the retigabine clinical trials, patients were experiencing seizures despite taking stable doses of up to three AEDs.
Retigabine has a different mechanism of action than currently approved AEDs. Retigabine is a neuronal potassium channel opener, which helps control neuronal excitability. In epilepsy patients, brain cells can become overly excited, disrupting normal brain activity and causing seizures.
"Approximately 30 percent of epilepsy patients are not well-controlled despite treatment with existing anti-epileptic drugs," said Jacqueline A. French, M.D., Professor of Neurology, New York University Medical Center and an investigator in the study. "Many of the currently available AEDs regulate sodium channels or calcium channels in the brain to help reduce seizures. Given the unmet medical need, it is hoped that medications with novel mechanisms of action, like retigabine, will improve outcomes in patients with refractory epilepsy."
About the Clinical Trials
The Phase III program for retigabine consisted of two randomized, double- blind, placebo-controlled, multi-center, parallel-group studies that assessed the efficacy, safety and tolerability of retigabine as an adjunctive treatment for adult epilepsy patients with refractory partial-onset seizures. The program, called RESTORE (Retigabine Efficacy and Safety Trial for Partial- Onset Epilepsy) 1 and 2, involved approximately 120 sites in more than 17 countries worldwide.
RESTORE 1 evaluated a 1200 mg daily dose of retigabine (the highest dose in the Phase III program) versus placebo, while RESTORE 2 evaluated 600 mg and 900 mg daily doses of retigabine versus placebo. In these studies, retigabine demonstrated a statistically significant reduction in seizures compared to placebo at all three doses when added to patients' current AED therapy. Additionally, RESTORE 2 showed a dose-dependent response when the dose of retigabine was increased from 600 mg to 900 mg daily.
Tolerability of retigabine was generally dose-dependent. The most common side effects associated with retigabine in the RESTORE trials occurring in greater than or equal to 10 percent of patients included dizziness, somnolence, fatigue, confusion, dysarthria (slurred speech), ataxia (loss of muscle coordination), urinary tract infection, blurred vision, tremor, and nausea. Urinary bladder effects, while monitored during the studies, were uncommonly reported.