Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

Huib A. Kerstjens*, Leif Bjermer, Leif Eriksson, Kerstin Dahlstrom, Jorgen Vestbo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Scopus)

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 300 mu g 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: 0.026 L, p = 0.69), morning PEF (-6 L/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 300 mu g 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. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1297-1303
Number of pages7
JournalRespiratory Medicine
Volume104
Issue number9
DOIs
Publication statusPublished - Sep-2010

Keywords

  • COPD
  • AZD4818
  • Chemokine receptor antagonist
  • Disease modification
  • CHEMOKINE RECEPTOR ANTAGONISTS
  • BX471
  • MICE
  • CP-481,715
  • DISEASES

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