Clinical trial NCT05051930: A Clinical Trial of TQC3721 Suspension for Inhalation
Official title: Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Primary Efficacy of TQC3721 Suspension for Inhalation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-21
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of adverse events
timeFrame: From the enrollment of the subjects to 72 hours after the last administration
measure: Incidence of adverse events
timeFrame: From the enrollment of the subjects to 72 hours after the last administration
measure: Number of adverse events related to the study drug
timeFrame: From the enrollment of the subjects to 72 hours after the last administration
measure: Incidence of adverse events associated with the study drug
timeFrame: From the enrollment of the subjects to 72 hours after the last administration
measure: Area Under The Curve（AUC）
timeFrame: Within 60 minutes before each administration, to 72 hours after administration
measure: Plasma drug peak concentration（Cmax ）
timeFrame: Within 60 minutes before each administration, to 72 hours after administration
measure: Time to peak（Tmax）
timeFrame: Within 60 minutes before each administration, to 72 hours after administration
Secondary outcomes:
measure: Elimination half-life time（t1/2）
timeFrame: Within 60 minutes before each administration, to 72 hours after administration
measure: Apparent volume of distribution（Vd）
timeFrame: Within 60 minutes before each administration, to 72 hours after administration
measure: Clearance（CL）
timeFrame: Within 60 minutes before each administration, to 72 hours after administration
measure: Forced Expiratory Volume in the first second (FEV1) for patients with Chronic Obstructive Pulmonary Disease（COPD） or asthma
timeFrame: From before administration to 3 hours after administration
measure: Mean Change From Baseline FEV1 to Morning Trough FEV1
timeFrame: From the enrollment of the subjects to to 72 hours after administration
measure: Mean Change From Baseline FEV1 to Average FEV1
timeFrame: From the enrollment of the subjects to to 72 hours after administration
measure: COPD Assessment Test (CAT) for patients with COPD
timeFrame: From enrollment to 4 weeks after administration
measure: Modified medical research council(mMRC) for patients with COPD or asthma
timeFrame: From enrollment to 4 weeks after administration
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
References: