Late Breaking Abstract - A Dose-Ranging Study of the Inhaled Dual PDE3/4 Inhibitor TQC3721 in COPD Patients

<bold>Background:</bold> TQC3721 is a novel dual phosphodiesterase (PDE)3 and PDE4 inhibitor with balanced bronchodilator and anti-inflammatory effects, developed for the treatment of Chronic Obstructive Pulmonary Disease (COPD). <bold>Objectives:</bold> The objective of this phase IIa clinical trial is to assess the safety and efficacy of TQC3721 in patients with COPD who are on a stable washing-out background therapy. <bold>Methods:</bold> A randomized, double-blind, placebo-controlled, multiple-ascending-dose study was conducted. Patients with moderate to severe COPD, with post-bronchodilator FEV₁ between 40-80% predicted, and FEV₁/FVC ratio ≤ 0.7 were included. They were randomized to receive one escalating doses of TQC3721 (BID: 0.75mg, 1.5mg, 3mg; QD: 1.5mg, 3mg, 6mg) or placebo. The primary endpoint was the change from baseline to week 4 in peak FEV₁ (maximum value during 3 hours post-dose). <bold>Results:</bold> A total of 75 patients were treated. Except for 0.75mg BID cohort, other cohorts of TQC3721 produced a significant and dose-dependent increase in peak FEV₁ from baseline to week 4, with differences of 152.8 ml (0.75 mg BID, <italic>P</italic>=0.543) to 246.8 ml (6mg QD， <italic>P</italic>=0.0025). A significant increase in average FEV₁ (0-12h) was shown at week 4 with 6mg QD dose (173.1 mL， <italic>P</italic>=0.0284，1.5mg and 3mg QD or BID does ranging from 122.6 to 127.9 mL). Clinically meaningful and numerically improvements in the COPD Assessment Test (CAT) were observed at week 4 in the 3mg QD and 6mg QD does. Adverse events were similar in frequency between the TQC3721 and placebo. <bold>Conclusion:</bold> In this study TQC3721 was well tolerated with rapid onset of action in 3 hours and lasting in 12 hours, supporting the regimen of 3mg and 6mg, twice daily for future trials.