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 (sGaw) 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 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 FEV1 effects than placebo. The average FEV1(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 sGaw showed greater RPL554 combination treatment effects versus monotherapy.
RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.
Abstract
The dual PDE3 and PDE4 inhibitor RPL554 causes additional bronchodilation when combined with commonly used short- or long-acting bronchodilators http://ow.ly/CUYi30lDcYW
Footnotes
This article has supplementary material available from erj.ersjournals.com
These studies are registered at www.clinicaltrials.gov with identifier numbers NCT02542254 and NCT03028142. This article contains considerable details of the group-level data. The protocol, statistical analysis plan and patient-level data can be accessed by contacting Verona Pharma plc.
Conflict of interest: D. Singh reports receiving personal fees from Verona during the conduct of the study; and personal fees from Apellis, Cipla, Genentech, Peptinnovate and Skyepharma, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Glenmark, Menarini, Merck, Mundipharma, Novartis, Pfizer, Pulmatrix, Teva, Therevance and Verona, outside the submitted work.
Conflict of interest: K. Abbott-Banner has nothing to disclose.
Conflict of interest: T. Bengtsson reports receiving personal fees for statistical consultancy from Verona Pharma plc during the conduct of the study and outside the submitted work.
Conflict of interest: K. Newman was previously an employee of Verona Pharma.
Support statement: This study was supported by Verona Pharma plc.
- Received June 8, 2018.
- Accepted August 22, 2018.
- Copyright ©ERS 2018.
This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.