Phase 2A Trial of ES-481, a Novel AMPA Receptor Antagonist, for Drug-Resistant Epilepsy

This double-blind, randomized, placebo-controlled trial evaluated ES-481, a selective TARP-γ8-dependent AMPA receptor antagonist, as an add-on therapy in 22 adults with drug-resistant epilepsy across Australian epilepsy centers. At the highest dose (75 mg twice daily), ES-481 showed 80% improvement in seizure frequency compared to 49% with placebo, with safety and tolerability assessments conducted alongside pharmacokinetic analysis.