Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
To evaluate the safety, tolerability and pharmacokinetic characteristics of TQC3721 suspension for inhalation in single/multiple administration(s) in healthy subjects; to evaluate the safety,tolerability and efficacy TQC3721 suspension for inhalation in multiple administrations in patients with Chronic Obstructive Pulmonary Disease（COPD）and asthma.
Interventions
Participants will receive 0.2 mg/1.0 mg/3.0 mg/6.0 mg/12.0 mg/24.0 mg single dose of TQC3721 suspension for inhalation.
Participants will receive 0mg single dose of TQC3721 suspension placebo for inhalation .
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Sign the informed consent form before the trial, fully understand the content, process and possible adverse reactions of the test; * Able to complete the study according to the requirements of protocol; * Aged between 18 and 65 years old, both men and women; * For healthy subjects: Male ≥50kg, female ≥45kg,body mass index(BMI)=weight (kg)/height 2 (m2), BMI is 18-28 kg/m2 (including the critical value); For patients: BMI is 18-28 kg/m2 (including the critical value), and body weight is ≥45kg. * For healthy subjects: normal or abnormal vital signs, physical examination, laboratory examination, electrocardiogram, and imageological examination have no clinical significance; * For healthy subjects: FEV1 and forced vital capacity(FVC) are at least 90% of the predicted values; * Subjects (including male 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; * For patients: Vital signs range: systolic blood pressure 90 to 140mmHg, diastolic blood pressure 50 to 90 mmHg, heart rate 50 to 90 bpm; * For patients: 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 (such as left band branch block, atrioventricular node dysfunction, ischemic ST segment abnormalities); * For patients: Ability to perform acceptable and reproducible spirometry; * For patients: According to the diagnostic criteria of 2018 Practical Edition of Guidelines for the Diagnosis and Treatment of COPD, the patient was diagnosed with COPD for at least 1 year;Post-bronchodilator spirometry at screening must demonstrate FEV1/FVC ratio of ≤0.70 and FEV1 must be ≥40 % to ≤80% of predicted normal; * For patients: mMRC Scoring at screening ≥2; * For patients: Clinically stable COPD in the previous 4 weeks; * For patients: Capable of withdrawing long acting bronchodilators until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study medication; * For patients: Current and former smokers with a smoking history of ≥10 pack years（smoking at least 20 cigarettes a day for 10 years or at least 10 cigarettes a day for 20 years）; * For patients: beta agonists are currently used only when needed; * For patients: Never smoked or An ex-smoker for ≥6 months；
Exclusion criteria
* Preexisting or existing the neuropsychiatric system, respiratory system, cardiovascular system, digestive system, hemo-lymphatic system, immune system, liver and kidney dysfunction, endocrine system, musculoskeletal system, or other disease that the investigator assesses that may affect drug metabolism or safety. * For healthy subjects: Have a history of fainting needles, fainting blood. * For healthy subjects: Known allergy to the study drug and their metabolites or any of the excipients of the formulation. * For healthy subjects: Those who smoked more than 5 cigarettes per day during the 3 months before the trial. * A history of alcohol abuse in the past 6 months (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). * For healthy subjects: Donated blood or had substantial loss of blood (more than 400 mL) within 2 months before the test. * For healthy subjects: Had taken any prescription, over-the-counter, vitamin product or herbal medicine within 1 month prior to the use of the study drug. * Participated in other clinical trials within 3 months prior to this study. * Positive for hepatitis (including hepatitis B and C), human immunodeficiency virus（HIV） or syphilis at screening. * Women who are pregnant or breast-feeding. * Positive test for alcohol. * For healthy subjects: Blood collection is difficult or cannot tolerate venipuncture blood collection. * For healthy subjects: The subject is unable or can not comply with ward management regulations. * For healthy subjects: The subject is unable to complete the study due to personal reasons. * For healthy subjects: Any circumstances that the investigator considers to pose a safety risk to the subject during the study or may interfere with the conduct of the study. * For patients: Intolerance to salbutamol, tiotropium, or this product or prior exposure to Ensifentrine (RPL554). * For patients: Use of any medicine within 4 weeks prior to initiation of the study drug, including non-prescription medications and herbs, except vitamins. * For patients: Physical examination findings that researchers consider clinically significant at the time of screening. * For patients: A history of cardiovascular disease (including arrhythmias) or active hyperthyroidism. * For patients: 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events | From the enrollment of the subjects to 72 hours after the last administration | The Number of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
| Incidence of adverse events | From the enrollment of the subjects to 72 hours after the last administration | The Incidence of adverse events as assessed by CTCAE v5.0 |
| Number of adverse events related to the study drug | From the enrollment of the subjects to 72 hours after the last administration | The number of adverse events associated with the study drug assessed by CTCAE V5.0 |
| Incidence of adverse events associated with the study drug | From the enrollment of the subjects to 72 hours after the last administration | Incidence of adverse events associated with the study drug as assessed by CTCAE V5.0 |
| Area Under The Curve（AUC） | Within 60 minutes before each administration, to 72 hours after administration | Area under the curve |
| Plasma drug peak concentration（Cmax ） | Within 60 minutes before each administration, to 72 hours after administration | Plasma drug peak concentration |
| Time to peak（Tmax） | Within 60 minutes before each administration, to 72 hours after administration | Time to maximum concentration following drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination half-life time（t1/2） | Within 60 minutes before each administration, to 72 hours after administration | Apparent terminal elimination half-life following drug administration |
| Modified medical research council(mMRC) for patients with COPD or asthma | From enrollment to 4 weeks after administration | Mean Change From Baseline in mMRC Scoring at Week 4.The severity is measured on a five-point scale from 0 to 4, with a higher score indicating more severe respiratory distress. |
| Apparent volume of distribution（Vd） | Within 60 minutes before each administration, to 72 hours after administration | Apparent volume of distribution |
| Clearance（CL） | Within 60 minutes before each administration, to 72 hours after administration | Clearance |
| Forced Expiratory Volume in the first second (FEV1) for patients with Chronic Obstructive Pulmonary Disease（COPD） or asthma | From before administration to 3 hours after administration | Mean Change From Baseline in Peak FEV1 (Over 3 Hours) |
| Mean Change From Baseline FEV1 to Morning Trough FEV1 | From the enrollment of the subjects to to 72 hours after administration | Mean Change From Baseline FEV1 to Morning Trough FEV1 |
| Mean Change From Baseline FEV1 to Average FEV1 | From the enrollment of the subjects to to 72 hours after administration | Mean Change From Baseline FEV1 to Average FEV1 |
| COPD Assessment Test (CAT) for patients with COPD | From enrollment to 4 weeks after administration | Mean Change From Baseline in COPD Assessment Test (CAT) Scoring at Week 4.The score range is 0 to 40 (0 to 10 is minor influence;11 to 20 is moderate; 21 to30 is severe;31 to 40 is very severe), and more than 10 indicates more symptoms. |
Countries
China
Contacts
Primary ContactWeimin Li, Post Doctor
Outcome results
None listed