Background: The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) are implicated in asthma pathogenesis. AMG 853 is a potent, selective, orally bioavailable, small-molecule dual antagonist of human D-prostanoid and CRTH2. Objective: We sought to determine the efficacy and safety of AMG 853 compared with placebo in patients with inadequately controlled asthma. Methods: Adults with moderate-to-severe asthma were randomized to placebo; 5, 25, or 100 mg of oral AMG 853 twice daily; or 200 mg of AMG 853 once daily for 12 weeks. All patients continued their inhaled corticosteroids. Long-acting ?-agonists were not allowed during the treatment period. Allowed concomitant medications included short-acting ?-agonists and a systemic corticosteroid burst for asthma exacerbation. The primary end point was change in total Asthma Control Questionnaire score from baseline to week 12. Secondary and exploratory end points included FEV1, symptom scores, rescue short-acting ?-agonist use, and exacerbations. Results: Among treated patients, no effect over placebo (n = 79) was observed in mean changes in Asthma Control Questionnaire scores at 12 weeks (placebo, ?0.492; range for AMG 853 groups [n = 317], ?0.444 to ?0.555). No significant differences between the active and placebo groups were observed for secondary end points. The most commonly reported adverse events were asthma, upper respiratory tract infection, and headache; 9 patients experienced serious adverse events, all of which were deemed unrelated to study treatment by the investigator. Conclusion: AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma.