Late Breaking Abstract - RPL554, a first-in-class dual PDE3/4 inhibitor, causes significant bronchodilation and symptom relief; a Phase 2b COPD study

Abstract

Introduction: RPL554 is an inhaled dual PDE3/4 inhibitor that showed bronchodilator and anti-inflammatory effects in prior clinical studies. This Phase 2b study investigated the effects and tolerability of RPL554 treatment for 4 weeks in moderate to severe COPD patients. Methods: This was a double-blind, placebo controlled, parallel group study. A total of 403 COPD patients (mean age 63.2 years) were enrolled. Patients were randomized to receive one of four doses of nebulised RPL554 (0.75mg, 1.5mg, 3mg, 6mg) or placebo twice daily. Spirometry was performed pre-dose and up to 12h post-dose at day 1 and week 4. Holter monitoring was performed. An electronic diary recorded daily symptoms (E-RS) and rescue salbutamol use. Results: 375 subjects (92.6%) completed the study. All RPL554 doses produced significant bronchodilation with an increase from baseline in peak FEV1 at week 4 of at least 200 mL (p 2 units). Salbutamol use was reduced (p Conclusions: RPL554 caused sustained bronchodilation over 4 weeks. There was a clinically and statistically significant and progressive improvement in COPD symptoms over the 4 weeks and reduction in rescue salbutamol use. The safety profile at all dose levels was similar to placebo.