Objectives. To evaluate the analgesic/antihyperalgesic effect of ASP8477. Design. Randomized, double-blind, double-dummy, cross-over, placebo- and active comparator-controlled study. Setting. HPR Dr. Schaffler GmbH, Munich, Germany. Subjects. Healthy female subjects aged 18-65 years. Methods. Eligible subjects were randomly assigned to one of six treatment sequences and received multiple ascending doses of ASP8477, duloxetine, and placebo over three treatment periods (each consisting of 21-day dosing separated by 14-day washout periods). On the last day of each dose level, laser evoked potentials (LEPs) and visual analog scales (VAS pain) on capsaicin-treated skin at baseline and at multiple postdose time points were assessed. The primary end point was the difference in LEP N2-P2 peak-to-peak (PtP) amplitudes for ASP8477 100mg vs placebo. Results. Twenty-five subjects were randomized. In all subjects, LEP N2-P2 PtP amplitudes were numerically lower for ASP8477 100mg vs placebo (P50.0721); in subjects who demonstrated positive capsaicin skin effects, a greater mean difference of -2.24 µV (P=0.0146) was observed. Across all doses, LEP N2-P2 PtP amplitudeswere lower for duloxetine compared with ASP8477 (mean difference -3.80 µV; P< 0.0001) or placebo (mean difference -5.21 µV; P< 0.0001). The effect of ASP8477 (all doses) on down-scoring the VAS pain score was significant compared with placebo (mean difference -2.55%; P< 0.0007). Conclusions. ASP8477 was well tolerated in this study. Analysis of all subjects did not demonstrate a significant difference in LEP for ASP8477 100mg over placebo but did in subjects who demonstrated positive capsaicin skin effects. [ABSTRACT FROM AUTHOR]