Abstract
Objectives ES-481 is an novel AMPA-Transmembrane AMPA regulatory protein (TARP) inhibitor that specifically targets hippocampal excitatory glutamate transmission by disrupting protein-protein interactions between the AMPA receptor and the γ-8 TARP. Preclinical data predicts that ES-481 has broad spectrum anti-seizure effects. ES-481-C201 is a Phase 2A trial in four Australian Epilepsy Clinical Trial Network (AECTN) centres assessing efficacy, safety and pharmacokinetics in adult patients with drug resistant epilepsy. It has two phases: Double-Blind Treatment (DBT) and Open-Label Extension (OLE). Here we report the early experience from the OLE.
Methods Subjects completing the DBT Phase are offered enrolment in the OLE. OLE subjects are assessed at regular intervals for anti-seizure efficacy and safety. Anti-seizure efficacy is assessed by examining mean difference in seizure frequency in the OLE to baseline in the DBT Phase. Safety is assessed by monitoring AEs and changes in blood parameters. To continue in OLE, subjects have to demonstrate continued efficacy, tolerability and safety measures.
Results To date, eight subjects have completed the DBT Phase and enrolled in the OLE. One subject dropped out due to a non-treatment AE, and one withdrew consent. The six remaining subjects have shown clinically significant decreases in seizure activity, good tolerability, and no adverse safety signals after 3 to 9 months.
Conclusions The data to date from the OLE Phase indicates that ES-481 is well tolerated and potentially efficacious in controlling seizures in adult subjects with drug resistant epilepsy. Confirmation of this experience is awaited from the results of the DBT Phase.
