title: Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients.
abstract: OBJECTIVE
  This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD.
  
  
  METHODS
  This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler((R)) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment.
  
  
  RESULTS
  Sixty-five patients (47 male; median age 65.6 years) received AZD4818 (n=33) or placebo (n=32). There was no statistically significant difference between AZD4818 and placebo in change from baseline to endpoint for FEV(1) (AZD4818-placebo: 0.026L, p=0.69), morning PEF (-6L/min, p=0.23), or other lung function measures. There was no difference between treatment groups in the 6-min walk test, MMRC dyspnoea index, BODE index and CCQ scores. Plasma concentrations indicated that patients were exposed to AZD4818 as expected. AZD4818 was well tolerated: 27 treatment-related adverse events (13 with AZD4818, 14 with placebo), 2 serious adverse events (both AZD4818: exacerbation [considered not treatment-related] and deep vein thrombosis [considered treatment-related]) and 11 discontinuations (7 with AZD4818).
  
  
  CONCLUSIONS
  Inhaled AZD4818 was well tolerated at 300mug twice daily for 4 weeks in patients with COPD; however, there was no indication of a beneficial treatment effect despite exposure as expected. These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas.
authors.affiliation: Department of Pulmonary Medicine, University of Groningen, Groningen, The Netherlands. h.a.m.kerstjens@long.umcg.nl
authors.forename: Huib A
authors.initials: HA
authors.lastname: Kerstjens
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Leif
authors.initials: L
authors.lastname: Eriksson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dahlström
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: C546512:AZD-4818; D001993:Bronchodilator Agents; D010880:Piperidines; D013141:Spiro Compounds