Effects of a Novel Dual Phosphodiesterase 3 and 4 Inhibitor TQC3721 in Patients With COPD in China (PACER-II): A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

Dual phosphodiesterase (PDE) 3 and 4 inhibitors have emerged as a novel therapeutic strategy for COPD, but their applicability remains limited to specific treatment contexts. To our knowledge, TQC3721 is a novel inhaled dual PDE3 and PDE4 inhibitor with synergistic bronchodilator and antiinflammatory effects. Dose TQC3721 improve lung function and symptoms in patients with COPD receiving background therapy with single or dual long-acting bronchodilators? This phase 2, randomized, double-blind, placebo-controlled trial (A Clinical Trial of TQC3721 Suspension for Inhalation in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease [PACER-II]) was conducted at 27 tertiary centers in China. Participants with after bronchodilator FEV₁ 30% to 70% of predicted and FEV₁/FVC < 0.7 were enrolled and randomized 1:1:1 to receive TQC3721 (3 or 6 mg) or placebo twice daily for 4 weeks. The primary end point was change of peak FEV₁ from baseline over 4 weeks. A total of 240 patients were randomized and treated, with 28.8% and 71.2% receiving concomitant long-acting muscarinic antagonists (LAMAs) or long-acting β₂-agonists (LABAs)/LAMAs, respectively. These results show that TQC3721 significantly improved peak FEV₁ at week 4 (3 mg group, 100 mL [95% CI, 41 to 159; P = .0011]; 6 mg group, 147 mL [95% CI, 93 to 201; P < .0001]) compared with placebo. Treatment with 6 mg TQC3721 significantly improved average FEV₁ area under the curve at 0 to 12 hours (87 mL; 95% CI, 43 to 131; P < .0001) and symptoms (St George's Respiratory Questionnaire score, -5.09; 95% CI, -8.44 to -1.74; P = .0031) vs placebo. Improvement of peak FEV₁ at week 4 in the LAMA (239 mL; 95% CI, 130 to 348; P < .0001) and LABA/LAMA (109 mL; 95% CI, 47 to 170; P = .0006) subgroups was superior to placebo following treatment with 6 mg TQC3721. The safety profile of TQC3721 was similar to that of placebo. TQC3721 significantly improved lung function and symptoms compared with placebo in patients with COPD receiving concomitant single or dual long-acting bronchodilators, with good tolerability. The study supports further development of TQC3721 in COPD. ClinicalTrials.gov; No.: NCT06527144; URL: www. gov.