An Open-Label Study Investigating the 5-HT_2A Receptor Occupancy of Remlifanserin (ACP-204) With the PET Radioligand...

Remlifanserin (ACP-204) is a selective 5-HT_2A receptor inverse agonist that builds upon scientific findings of its structural analog, pimavanserin. This Phase 1, open-label study in healthy adults (N = 16) describes the central 5-HT_2A receptor occupancy of remlifanserin at different doses and plasma concentrations using positron emission tomography imaging and radioligand [¹⁸F]altanserin, with pimavanserin as a reference molecule. Receptor occupancy measurements taken at time to maximum plasma concentration (T_max) and various intervals up to five half-lives after T_max were correlated with study drug plasma concentrations and estimated from a Lassen plot. Administration of remlifanserin or pimavanserin resulted in plasma-concentration-dependent occupancy of 5-HT_2A receptors (ranges, 53%-100% and 41%-100%, respectively) and was adequately predicted by an E_max model with a fixed Hill slope of 1. The half maximal effective plasma concentration (EC₅₀) values for remlifanserin and pimavanserin were estimated to be 0.37 and 0.55 ng/mL, respectively, suggesting that remlifanserin occupies 5-HT_2A receptors with comparable to slightly greater potency than pimavanserin. Single doses of remlifanserin were safe and well tolerated. Study findings will inform the development and dosing of remlifanserin in future Phase 2/3 trials.