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Introduction: AZD8871 is an inhaled long-acting dual muscarinic antagonist/β2 adrenoceptor agonist (MABA) for COPD/asthma. This randomized, double-blind 3-way complete crossover trial (NCT02971293) assessed the efficacy and pharmacokinetics of AZD8871. 42 patients, with moderate to severe reversible COPD, received once-daily doses of AZD8871 100µg, 600µg or placebo via a dry powder inhaler device for 14 days. The primary endpoint was change from baseline (CFB) trough FEV1 on Day (D)15. Wash-out periods were 28–35 days. Results: On D15, least square (LS) mean CFB (95% CI) differences in trough FEV1, for AZD8871 100µg and 600µg versus placebo, were 161(75–246) and 260(176–343)mL, respectively. Substantial symptomatic improvements, measured by breathlessness, cough and sputum scale, were observed on D14 for AZD8871 600µg versus placebo (LS mean =-1.162). On D9–14, CFB rescue medication use improved for AZD8871 600µg (p Reportable plasma concentration data for PK analysis were received from 18 patients. AZD8871 was rapidly absorbed (median tmax range 0.9 to 1.5hours). The exposure increased in an approximately dose proportional manner on D14 with 5.3- and 5.9- fold increases for Cmax and AUC(0-24), respectively, for the 6-fold increase in dose. Accumulation ratios on D14 were similar for both dose levels with 1.3-fold increase in Cmax and 1.8-fold increase in AUC(0-24). Conclusion: AZD8871 doses delivered significant bronchodilation with clinically meaningful improvement on symptoms. AZD8871 exposure was approximately dose proportional and accumulated after repeated doses. |
