A Phase II Clinical Trial of TQC3721 Suspension for Inhalation

A Randomized, Double-blind, Placebo-parallel, Multicenter Phase II Trial of the Efficacy and Safety of TQC3721 Suspension for Inhalation in the Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease

TQC3721 suspension for inhalation is a PDE3/4 inhibitor developed by Chia Tai Tianqing Pharmaceutical Group Co., LTD., which can simultaneously achieve bronchial smooth muscle relaxation and anti-inflammatory effects. This is a randomized, double-blind, placebo-parallel, phase II trial of the efficacy and safety of inhaled TQC3721 suspension/placebo at different doses in patients with moderate to severe chronic obstructive pulmonary disease. Objective To evaluate the efficacy, safety and tolerability of TQC3721 inhalation suspension in the treatment of moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

Inclusion Criteria:

• 1 Sign the informed consent form before the trial, fully understand the content, process and possible adverse reactions of the test;
• 2 Capable of using the study nebulizer correctly and complying with all study restrictions and procedures;
• 3 Aged between 18 and 75 years old, both men and women;
• 4 Body mass index(BMI)=weight (kg)/height 2 (m2), BMI is 18-28 kg/m2 (including the critical value) and body weight is ≥45kg;
• 5 Subjects have no pregnancy plan and have voluntarily taken effective contraceptive measures for at least 1 month after being screened to the last use of the study drug;
• 6 12-lead electrocardiogram with QT interval corrected ≤450 msec (males) or ≤470 msec (females), QRS interval ≤120 msec, PR interval ≤200 msec and no morphologic and other clinical significant abnormalities that the investigator considered inappropriate for the study;
• 7 Ability to perform acceptable and reproducible spirometry;
• 8 Patients previously treated with LAMA or LABA who had evidence of stable use for at least 3 months prior to screening and agreed to continue use during the study period;
• 9 Capable of withholding LAMA or LABA（ Twice-Daily maintenance LAMA or LABA for at least 24 hours and Once-Daily maintenance LAMA or LABA for at least 48 hours) and SAMA、SABAs（at least 4 hours）prior to initiation of any spirometry;
• 10 According to the 2020 GOLD Guidelines, Post-bronchodilator spirometry at screening must demonstrate FEV1/FVC ratio of ≤0.70 and FEV1 must be ≥30 % to ≤80% of predicted normal;
• 11 Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years, former cigarette smokers should stop smoke at least 6 months before visit 1).

Exclusion Criteria:

• 1 Intolerance to salbutamol or this product.
• 2 ≥1 hospitalization for COPD treatment within 6 months prior to screening.
• 3 Antibiotic treatment for lower respiratory tract infection within 3 months prior to screening.
• 4 Use of prohibited medications within the time intervals.
• 5 Patients who were currently diagnosed with asthma, active tuberculosis, lung cancer and other active lung diseases and were considered unsuitable for the study.
• 6 Previous lung resection or lung reduction surgery.
• 7 Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.
• 8 A history of drug or alcohol abuse in the past 3 years (14 units of alcohol consumed per week: 1 unit =360 ml of beer or 45 ml of 40% alcohol spirits or 150 ml of wine).
• 9 Have participated in a clinical trial within one month prior to screening or within 5 half-lives of the investigational drug, whichever is the longer.
• 10 Women who are breast-feeding.
• 11 A history of myocardial infarction, congestive heart failure, and unstable or uncontrolled hypertension (systolic blood pressure ≥160mmHg and diastolic blood pressure ≥100mmHg after drug control) within 6 months prior to screening.
• 12 History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin.
• 13 Alanine aminotransferase (ALT) or aspartate aminotransferase(AST)≥ 2 x upper limit of normal (ULN), or other abnormal test results were deemed unsuitable for inclusion by the investigator.
• 14 Required use of oxygen therapy, even on an occasional basis.
• 15 Other conditions that the investigator considered inappropriate for participation in the study.