Pharmacodynamics Studies providing pharmacodynamic data Table 12 shows the studies relating to each pharmacodynamic topic. 12. Submitted pharmacodynamic studies. PD Topic Subtopic ID Primary In male COPD patients M/34273/21 pharmacology: To characterise PIF generated through Novolizer Secondary and the Handihaler dry powder inhalers by COPD Pharmacology patients Effect on QT intervals Gender other Effect of gender None genetic and Age-Related Effect of age None Differences in PD Response PD Interactions Not evaluated None Population PD Healthy subjects Not and PK-PD applicable analyses Target population None None of the pharmacodynamic studies had deficiencies that excluded their results from consideration. Summary of pharmacodynamics The information in the following summary is derived from conventional pharmacodynamic studies in humans unless otherwise stated. Mechanism of action Aclidinium bromide is a competitive, selective muscarinic receptor antagonist (also known as an anticholinergic) with a longer residence time at the M3 receptors than the M2 receptors. M3 receptors mediate contraction of airway smooth muscle. Inhaled aclidinium bromide acts locally in the lungs to antagonise M3 receptors of airway smooth muscle and induce bronchodilation. Nonclinical in vitro and studies showed rapid, dose-dependent and long-lasting in vivo inhibition by aclidinium bromide of acetylcholine-induced bronchoconstriction. Aclidinium bromide is quickly broken down in plasma and the level of systemic anticholinergic side effects is therefore low. The affinity of aclidinium bromide, LAS34823 and LAS34850 for various receptors and enzymes was studied in radioligand binding assays and enzymatic studies, respectively. Aclidinium bromide showed only moderate affinity (IC50 1 on ≥ μM) (α)1 (non-selective) receptors, histaminergic (H)1 (central) receptor, Neurokinin (NK)1 receptors and had moderate inhibitory effects on 5-hydroxytryptamine (5-HT) uptake, in
Pharmacodynamics Studies providing pharmacodynamic data Table 12 shows the studies relating to each pharmacodynamic topic. 12. Submitted pharmacodynamic studies. PD Topic Subtopic ID Primary pharmacology: Secondary Pharmacology In male COPD patients To characterise PIF generated through Novolizer and the Handihaler dry powder inhalers by COPD patients Effect on QT intervals M/34273/21 Gender other genetic and Age-Related Differences in PD Response Effect of gender None Effect of age None PD Interactions Not evaluated None Population PD and PK-PD analyses Healthy subjects Not applicable Target population None None of the pharmacodynamic studies had deficiencies that excluded their results from consideration. Summary of pharmacodynamics The information in the following summary is derived from conventional pharmacodynamic studies in humans unless otherwise stated. Mechanism of action Aclidinium bromide is a competitive, selective muscarinic receptor antagonist (also known as an anticholinergic) with a longer residence time at the M3 receptors than the M2 receptors. M3 receptors mediate contraction of airway smooth muscle. Inhaled aclidinium bromide acts locally in the lungs to antagonise M3 receptors of airway smooth muscle and induce bronchodilation. Nonclinical in vitro and in vivo studies showed rapid, dose-dependent and long-lasting inhibition by aclidinium bromide of acetylcholine-induced bronchoconstriction. Aclidinium bromide is quickly broken down in plasma and the level of systemic anticholinergic side effects is therefore low. The affinity of aclidinium bromide, LAS34823 and LAS34850 for various receptors and enzymes was studied in radioligand binding assays and enzymatic studies, respectively. Aclidinium bromide showed only moderate affinity (IC50 ≥ 1 μM) on (α)1 (non-selective) receptors, histaminergic (H)1 (central) receptor, Neurokinin (NK)1 receptors and had moderate inhibitory effects on 5-hydroxytryptamine (5-HT) uptake, in
auspar-aclidinium-bromide-140908-cer.docx