The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD

Abstract

We investigated the short-term bronchodilator effects of RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined with other bronchodilators in chronic obstructive pulmonary disease patients with reversibility (>150 mL to short-acting bronchodilators).Study 1 was a six-way, placebo-controlled crossover study (n=36) with single doses of RPL554 (6 mg), salbutamol (200 µg), ipratropium (40 µg), RPL554 (6 mg)+salbutamol (200 µg), RPL554 (6 mg)+ipratropium (40 µg) or placebo. Study 2 was a three-way crossover study (n=30) of tiotropium (18 µg) combined with RPL554 (1.5 or 6 mg) or placebo for 3 days. Forced expiratory volume in 1 s (FEV₁), lung volumes and specific airway conductance (s<i>G</i> _aw) were measured.In study 1, peak FEV₁ change compared with placebo was similar with RPL554, ipratropium and salbutamol (mean 223, 199 and 187 mL, respectively). The peak FEV₁ was higher for RPL554+ipratropium <i>versus</i> ipratropium (mean difference 94 mL; p<0.0001) and RPL554+salbutamol <i>versus</i> salbutamol (mean difference 108 mL; p<0.0001). In study 2 (day 3), both RPL554 doses caused greater peak FEV₁ effects than placebo. The average FEV₁ _{(0-12 h)} increase was greater with RPL554 6 mg only <i>versus</i> placebo (mean difference 65 mL; p=0.0009). In both studies, lung volumes and s<i>G</i> _aw showed greater RPL554 combination treatment effects <i>versus</i> monotherapy.RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.