A Clinical Trial of TQC3721 Suspension for Inhalation

Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Primary Efficacy of TQC3721 Suspension for Inhalation

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: TQC3721 suspension for inhalation; Drug: TQC3721 suspension placebo for inhalation

• Study Type: Interventional
• Enrollment (Anticipated): 114
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Weimin Li, Post Doctor; Phone Number: 028-85423837; Email: llllllv2@126.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Weimin Li, Post Doctor; Phone Number: 028-85423837; Email: llllllv2@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TQC3721 suspension for inhalation; 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 on Day 1.	Drug: TQC3721 suspension for inhalation; 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.
PLACEBO_COMPARATOR: TQC3721 suspension placebo for inhalation; Participants will receive 0mg single dose of TQC3721 suspension placebo for inhalation on Day 1.	Drug: TQC3721 suspension placebo for inhalation; Participants will receive 0mg single dose of TQC3721 suspension placebo for inhalation .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	The Number of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	From the enrollment of the subjects to 72 hours after the last administration
Incidence of adverse events	The Incidence of adverse events as assessed by CTCAE v5.0	From the enrollment of the subjects to 72 hours after the last administration
Number of adverse events related to the study drug	The number of adverse events associated with the study drug assessed by CTCAE V5.0	From the enrollment of the subjects to 72 hours after the last administration
Incidence of adverse events associated with the study drug	Incidence of adverse events associated with the study drug as assessed by CTCAE V5.0	From the enrollment of the subjects to 72 hours after the last administration
Area Under The Curve（AUC）	Area under the curve	Within 60 minutes before each administration, to 72 hours after administration
Plasma drug peak concentration（Cmax ）	Plasma drug peak concentration	Within 60 minutes before each administration, to 72 hours after administration
Time to peak（Tmax）	Time to maximum concentration following drug administration	Within 60 minutes before each administration, to 72 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elimination half-life time（t1/2）	Apparent terminal elimination half-life following drug administration	Within 60 minutes before each administration, to 72 hours after administration
Apparent volume of distribution（Vd）	Apparent volume of distribution	Within 60 minutes before each administration, to 72 hours after administration
Clearance（CL）	Clearance	Within 60 minutes before each administration, to 72 hours after administration
Forced Expiratory Volume in the first second (FEV1) for patients with Chronic Obstructive Pulmonary Disease（COPD） or asthma	Mean Change From Baseline in Peak FEV1 (Over 3 Hours)	From before administration to 3 hours after administration
Mean Change From Baseline FEV1 to Morning Trough FEV1	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 Average FEV1	Mean Change From Baseline FEV1 to Average FEV1	From the enrollment of the subjects to to 72 hours after administration
COPD Assessment Test (CAT) for patients with COPD	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.	From enrollment to 4 weeks after administration
Modified medical research council(mMRC) for patients with COPD or asthma	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.	From enrollment to 4 weeks after administration

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 18, 2021
• Primary Completion (ANTICIPATED): October 31, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: September 12, 2021
• First Posted (ACTUAL): September 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: TQC3721-I-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No