AZD8871 delivered significant bronchodilation in two-week study

SAN DIEGO – The investigational agent AZD8871 at once daily doses of 100 mcg and 600 mcg led to statistically significant, clinically relevant, and dose-ordered differences in trough FEV₁ at two weeks compared with placebo, results from a phase 2a trial showed.

AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”

^{Doug Brunk/MDedge News}

Dr. Dave Singh

Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV₁.

For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”

The primary efficacy endpoint was change from baseline trough FEV₁ on day 15. Secondary endpoints included change from baseline in peak FEV₁, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.

At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV₁ was about 58% predicted, and their FEV₁ absolute reversibility was a mean of 379 mL, “which is rather high,” he said.

Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV_1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV₁ for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.