TY - JOUR
T1 - Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients
AU - Kerstjens, Huib A
AU - Bjermer, Leif
AU - Eriksson, Leif
AU - Dahlström, Kerstin
AU - Vestbo, Jørgen
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1016/j.rmed.2010.04.010
DO - 10.1016/j.rmed.2010.04.010
M3 - Journal article
C2 - 20466530
SN - 0954-6111
VL - 104
SP - 1297
EP - 1303
JO - Respiratory medicine
JF - Respiratory medicine
IS - 9
ER -