Amorphous solid dispersions (ASD) of a poorly soluble water-soluble VR1 antagonist (AMG 517) were explored for improving physical stability and in vivo exposure. AMG 517 was incorporated at 15 or 50 wt % into polymeric microparticles of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and hydroxypropyl methylcellulose (HPMC) by spray-drying. Solid particles having a collapsed, corrugated structure were observed by SEM. Median particle size ranged from 29 to 40 μm by laser light scattering, and residual solvent levels were below 2% by thermal gravimetric analysis. ASD powders exhibited single glass transition temperatures (T g) in the range of 98−117 °C by modulated DSC and were amorphous by XRPD. Amorphous stability, characterized at 40 °C/75% RH (open dish) by XRPD, was at least six months for ASD formulations. Drug dissolution and supersaturation testing in a USP-2 apparatus indicated superior performance of ASD formulations over micronized AMG 517. PK of an ASD formulation in capsule (15 wt % AMG 517 in HPMCAS blended with 5 wt % SDS) in cynomolgus monkeys (n = 6, crossover) increased AUC 163% and C max 145% in comparison to an OraPlus suspension control. The study demonstrates the ASD approach provides improved amorphous physical stability and oral bioavailability for a poorly soluble development-stage molecule.