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AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthma patients improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomized and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic patients with COPD (average pre-bronchodilator forced expiratory volume in one-second (FEV1) at screening was 50-52% of predicted normal). Pre-bronchodilator FEV1 was primary variable, with other lung function parameters plus symptoms and 24-hr plasma cortisol being secondary variables. Plasma concentrations of AZD5423 were also measured. Effects were compared against placebo and a reference glucocorticoid receptor agonist control. Neither AZD5423, at doses which have shown to be efficacious in allergen-induced asthma, nor the reference control, at double the approved dose, had any clinically meaningful effect in the patient population studied in regard to lung function or markers of inflammation. Both GR modulators were well tolerated and did suppress 24-hr cortisol. This study suggests that the selected population of patients with COPD does not respond to treatment with AZD5423 as regards lung function, while showing the expected systemic effects. It cannot be ruled out that a favourable lung function response of AZD5423 can be evoked using another experimental setting and/or within a different population of patients with COPD., (© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)