Ensifentrine, A Novel Dual Phosphodiesterase (Pde) 3 And 4 Inhibitor, Provides Effective Bronchodilation When Administered By Metered Dose Inhaler In Patients With Copd

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Ensifentrine (RPL554) is an investigational, first-in-class, inhaled dual inhibitor of PDE 3 and 4 that combines bronchodilator and anti-inflammatory actions in a single compound. In previous trials, nebulised ensifentrine delivered clinically meaningful and significant improvements vs placebo in lung function and symptoms in COPD. METHODS: This phase 2, randomized, parallel group, double blind, placebo controlled, single dose study reports the effect of ensifentrine administered by pressurized metered dose inhaler (pMDI) in patients with moderate to severe chronic obstructive pulmonary disease (COPD). The primary objective was to investigate the pharmacokinetic profile of a single dose of ensifentrine (100, 300, 1000, 3000 or 6000 mcg) or placebo administered by pMDI. Secondary objectives included effects of single doses of ensfentrine on safety, tolerability and FEV1 versus placebo. Patients demonstrated post-bronchodilator (4 puffs of salbutamol) FEV1/FVC ratio ≤0.70, FEV1≥40% and ≤80% of predicted normal and ≥150 mL increase from pre-bronchodilator FEV1. Serial spirometry was performed at 0-12 hours. ECGs were performed pre- and post dose over 8 hours, with vital signs collected over 24 hours. RESULTS: We examined 40 patients (n=6 in the 100 and 1000 mcg groups; n=7 in the other groups) from two U.K. sites. Overall mean age was 66.3 years with 60% male patients. After a single dose, ensifentrine provided a dose-dependent, significant and clinically meaningful bronchodilator response, in terms of the mean change from baseline in peak FEV1 over 4 hours with the four highest doses (placebo-corrected values, 300 mcg: 178 mL (p=0.0098); 1000 mcg: 169 mL (p=0.0295): 3000 mcg: 246 (p=0.0022); 6000 mcg: 391 mL (p<0.0001). Average FEV1 0-4 hours showed similar results to peak FEV1 and the profile demonstrated sustained bronchodilation over 12 hours. CONCLUSIONS: No significant adverse events were reported. Headache was reported in 2/7 patients in the 6000 mcg dose. A small but statistically significant increase in peak heart rate was observed with the 3000 and 6000 mcg doses of 7 bpm and 11 bpm, respectively. CLINICAL IMPLICATIONS: This study demonstrates that ensifentrine administered by pMDI delivered a well tolerated, rapid and meaningful bronchodilatory response following a single dose that was sustained for 12 hours. Ensifentrine administered via pMDI may be an effective and convenient treatment for patients with COPD. DISCLOSURES: Consultant relationship with Verona Pharma Please note: $5001 - $20000 Added 06/01/2020 by Thomas Bengtsson, source=Web Response, value=Consulting fee No relevant relationships by brian leaker, source=Web Response Employee relationship with Verona pharma Please note: >$100000 by Tara Rheault, source=Admin input, value=Stock Employee relationship with Verona Pharma Please note: >$100000 Added 05/20/2020 by Kathleen Rickard, source=Web Response, value=Salary Consultant relationship with AstraZeneca Please note: $20001 - $100000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with Chiesi Please note: $20001 - $100000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with Novartis Please note: $1001 - $5000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with Boehinger Please note: $5001 - $20000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with GSK Please note: $5001 - $20000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with Menaini Please note: $5001 - $20000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with Therevance Please note: $1001 - $5000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee Consultant relationship with Cipla Please note: $1001 - $5000 Added 03/23/2020 by Dave Singh, source=Web Response, value=Consulting fee