A randomized placebo and active controlled trial of AZD8871 a novel dual acting bronchodilator in COPD patients

AZD8871 is an inhaled long acting dual muscarinic antagonist/β 2 adrenoceptor agonist (MABA) under development for treatment of COPD and asthma. This 5-way complete crossover trial was designed to test efficacy, pharmacokinetics, safety and tolerability of AZD8871 in patients with COPD. Moderate to severe COPD patients ≥40 years of age (females of non-childbearing potential and males) were randomized. Patients received single doses of AZD8871 400 or 1800 µg, or placebo in a double blind fashion, or open label indacaterol 150 µg or tiotropium 18 µg, in a randomized order. Each treatment was followed by a wash out period of 7-21 days. 38 patients were randomized and 28 patients completed all treatments. Mean (SD) %predicted FEV 1 at baseline was 52(12.5)% and 20(13.7)% patients were reversible. AZD8871 pharmacokinetics were assessed in subset of 18 patients. AZD8871 demonstrated very quick onset of action, within 5 min of dosing, at both doses. A sustained bronchodilation over 36 hours was observed with both doses of AZD8871. LS mean (SEM) differences in Trough FEV 1 for AZD8871 400 µg u0026 1800 µg, indacaterol and tiotropium versus placebo were 107(24), 210(24), 153(24), 138(24) mL, respectively. AZD8871 1800 µg showed greater bronchodilation than both indacaterol and tiotropium for both peak and trough FEV 1 . Few adverse events were observed: headache (31.6%) and nasopharyngitis (13.2%) were the most common and there was no dose response observed with any adverse event. Overall, both dose levels of AZD8871 delivered significant and sustained bronchodilation, superior to placebo and at the highest dose superior to both reference agents, with no emerging safety concerns.