title: Efficacy and safety of AZD1981, a CRTH2 receptor antagonist, in patients with moderate to severe COPD.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of the selective CRTh2 (DP2) receptor antagonist AZD1981 compared with placebo in patients with moderate to severe COPD.
  
  
  METHODS
  In this multicentre, randomised, double-blind, parallel-group, phase IIa study (ClinicalTrials.gov identifier: NCT00690482) patients with moderate to severe COPD received either AZD1981 1000 mg twice daily or matching placebo for 4 weeks. Inhaled terbutaline was used as-needed as reliever medication throughout. The co-primary endpoints were change from baseline to end of treatment in pre-bronchodilator forced expiratory volume in 1 s [FEV1] and the Clinical COPD Questionnaire (CCQ). Additional endpoints included other lung function measures, 6-min walk test (6-MWT), COPD symptom score, reliever medication use and tolerability.
  
  
  RESULTS
  118 patients were randomised to treatment (AZD1981 n = 61; placebo n = 57); 83% of patients were male and the mean age was 63 years (range 43-83). There were no significant differences in the mean difference in change from baseline to end of treatment between AZD1981 and placebo for the co-primary endpoints of pre-bronchodilator FEV1 (AZD1981-placebo: -0.015, 95% CI: -0.10 to 0.070; p = 0.72) and CCQ total score (difference: 0.042, 95% CI: -0.21 to 0.30; p = 0.75). Similarly, no differences were observed between treatments for the other outcomes of lung function, COPD symptom score, 6-MWT, BODE index, and use of reliever medication. AZD1981 was well tolerated.
  
  
  CONCLUSIONS
  There was no beneficial clinical effect of AZD1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD1981 was well tolerated and no safety concerns were identified.
authors.affiliation: The Royal Brompton Hospital and National Heart & Lung Institute, London SW3 6NP, UK. Electronic address: n.snell@rbht.nhs.uk.
authors.forename: Noel
authors.initials: N
authors.lastname: Snell
authors.forename: Martyn
authors.initials: M
authors.lastname: Foster
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
mesh_terms: D000085:Acetates / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000085:Acetates; D001993:Bronchodilator Agents; D007211:Indoles; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C569518:AZD1981; C036293:prostaglandin D2 receptor
keywords: AZD1981; COPD; CRTh2 antagonist