title: Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients.
abstract: BACKGROUND
  The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on T(H)2 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 β-agonists were not allowed during the treatment period. Allowed concomitant medications included short-acting β-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 FEV(1), symptom scores, rescue short-acting β-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wis, USA. Wwb@medicine.wisc.edu
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: Eli O
authors.initials: EO
authors.lastname: Meltzer
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.forename: Mark C
authors.initials: MC
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Chon
authors.forename: Alison L
authors.initials: AL
authors.lastname: Budelsky
authors.forename: Joseph
authors.initials: J
authors.lastname: Lin
authors.forename: Shao-Lee
authors.initials: SL
authors.lastname: Lin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010648:Phenylacetates / Q000009:adverse effects / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012129:Respiratory Function Tests; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D010648:Phenylacetates; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C573852:vidupiprant; C036293:prostaglandin D2 receptor