Key result
RPL554 combined with ipratropium or salbutamol significantly increased peak FEV1 compared to monotherapy (mean difference 94 mL and 108 mL, respectively; both p<0.0001).
Why the study?
Does RPL554 combined with standard bronchodilators improve lung function in patients with COPD?
RCT (n=66)
Does RPL554 combined with standard bronchodilators improve lung function in patients with COPD?
Mean Difference: 94
p-value: p=<0.0001
RPL554 combined with standard bronchodilators provides additional bronchodilation and reduces hyperinflation in patients with COPD.
RPL554 may add bronchodilation to salbutamol or ipratropium in COPD; extends PDE3/4 inhibition evidence for adjunctive use.
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 (FEV 1 ), lung volumes and specific airway conductance (s G aw ) were measured. In study 1, peak FEV 1 change compared with placebo was similar with RPL554, ipratropium and salbutamol (mean 223, 199 and 187 mL, respectively). The peak FEV 1 was higher for RPL554+ipratropium versus ipratropium (mean difference 94 mL; p<0.0001) and RPL554+salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). In study 2 (day 3), both RPL554 doses caused greater peak FEV 1 effects than placebo. The average FEV 1 (0–12 h) increase was greater with RPL554 6 mg only versus placebo (mean difference 65 mL; p=0.0009). In both studies, lung volumes and s G aw showed greater RPL554 combination treatment effects versus monotherapy. RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.
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Singh et al. (2018) conducted an RCT in chronic obstructive pulmonary disease (n=66). RPL554 vs. placebo, salbutamol, ipratropium, and tiotropium was evaluated on peak FEV1 (MD 94 mL, p=<0.0001). RPL554 combined with ipratropium or salbutamol significantly increased peak FEV1 compared to monotherapy (mean difference 94 mL and 108 mL, respectively; both p<0.0001).
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