| Eligibility |
Inclusion Criteria:
1. Male or female participants who can understand and are willing to complete this trial
in strict accordance with the clinical trial protocol, and voluntarily sign the
informed consent form;
2. Age = 18 years (subject to the age specified in the valid document at the time of
signing the informed consent form);
3. Male participants weighing = 50 kg and female participants weighing = 45 kg, and BMI <
35kg/m2;
4. History of chronic cough for more than 1 year, and definitely diagnosed as refractory
chronic cough or chronic cough of unknown cause. See Appendix 2 for the diagnostic
criteria;
5. Chest imaging within 5 years prior to screening and after the onset of chronic cough
did not show abnormal changes that in the opinion of the investigator may contribute
to the chronic cough;
6. The 100-mm cough Visual Analogue Scale (VAS) score = 40 mm at screening and baseline;
7. The cough recorder at screening showed an average of 10 or more coughs per hour while
awake;
8. Participants of childbearing potential and their sexual partners are willing to take
one or more effective non-drug contraceptive measures and have no plans to donate
sperm or ova from the time of screening until 6 months after the last dose of study
drug; Female participants should be non-pregnant and non-lactating, and should meet at
least 1 of the following conditions:
1. Not a woman of childbearing potential (WOCBP) as defined in the appendix;
2. Is a WOCBP and agrees to follow the contraception requirements in the appendix
for the duration of the study and for at least 6 months after the last dose of
the study;
3. The WOCBP has a negative blood pregnancy test prior to the first dose of study
drug;
4. If the blood pregnancy result is positive, the participant must be withdrawn from
the study;
5. Refer to the Study Flow Chart for additional pregnancy testing requirements
during and after the study;
6. Investigators are responsible for reviewing medical and menstrual history to see
whether the requirements for highly effective contraception will be met so as to
reduce the risk of including females with early undetected pregnancy.
Exclusion Criteria:
1. Pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity
(FVC) < 70% of the expected value at screening;
2. History of upper or lower respiratory tract infection (including bacterial, fungal,
viral and other pathogenic microorganism infections) or recent significant change in
pulmonary conditions (including acute exacerbation of respiratory disease or
significant change in chest imaging) within 4 weeks prior to screening or
randomization;
3. Diagnosed as chronic obstructive pulmonary disease (COPD), bronchiectasis, idiopathic
pulmonary fibrosis (IPF), active pulmonary tuberculosis before screening;
4. Past medical history of hypogeusia or taste disorder, or known taste abnormality;
5. With malignancy within 5 years prior to screening (except adequately treated basal
cell or squamous cell skin cancer or cervical carcinoma in situ);
6. Moderate renal insufficiency: glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
prior to screening or prior to randomization;
7. Moderate to severe hepatic insufficiency (Child-Pugh Class B or C) prior to screening
or prior to randomization;
8. History of unstable or worsening cardiovascular disease prior to screening or prior to
randomization, including but not limited to: unstable angina, myocardial infarction,
thromboembolism;
9. Those who are smoking or have quitted smoking for less than 1 year, or have a smoking
history of annual consumption of more than 20 pack-years at screening;
10. Recent (within the past 1 year) history of drug or alcohol abuse or dependence;
11. Known hypersensitivity to any ingredient of this medication;
12. Systemic or topical use of drugs or foods that may affect the PK characteristics of
the study drug, including strong inducers, strong inhibitors or substrates of CYP2C19
and CYP3A, and drinking grapefruit or grapefruit juice within 14 days prior to
screening and during the trial (see Table 6 for details);
13. Systemic or topical use of antitussive drugs, including opioids, pregabalin,
gabapentin, dextromethorphan, traditional Chinese medicine and over-the-counter drugs
with antitussive effect, etc., within 4 weeks prior to screening and during the trial
[participants are allowed to receive a stable (= 4 weeks prior to the first dose of
study drug) treatment for cough etiology, including antihistamines, leukotriene
receptor antagonists, inhaled or oral glucocorticoids, long-acting bronchodilators,
etc., or receive stable (= 8 weeks prior to the first dose of study drug) treatment
with proton pump inhibitors];
14. Receiving an angiotensin converting enzyme inhibitor currently or within 3 months
prior to screening;
15. Participation in any other clinical study with the last dose of an study drug within 4
weeks prior to screening, or within 5 half-lives at screening (whichever is longer);
16. Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening
and baseline (the test should be performed after resting for at least 5 minutes and
the criterion is still met after a repeat examination);
17. Family history of long QT syndrome and sudden death, or significant ECG abnormalities
at screening, including but not limited to: QTcF interval > 450 ms, atrial
fibrillation or flutter, heart rate < 40 beats/min or > 110 beats/min, second or third
degree atrioventricular block, left bundle branch block;
18. Clinically significant abnormalities in laboratory test results at screening,
including but not limited to:
1. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
phosphatase (ALP) or glutamyl transpeptidase (GGT) > 2 times the upper limit of
normal, and total bilirubin > 1.5 times the upper limit of normal;
2. Creatinine > times the upper limit of normal;
3. Coagulation abnormalities including but not limited to abnormal platelet count (<
100 × 103/mm3), prolonged PT or INR = 1.5;
19. Positive hepatitis B virus surface antigen, or positive hepatitis B virus core
antibody, negative hepatitis B virus surface antibody and positive HBV-DNA, or
positive hepatitis C virus antibody or positive HCV-RNA, or positive treponema
pallidum antibody, or positive human immunodeficiency virus (HIV) antibody at
screening;
20. Pregnant or breast-feeding;
21. Any past or current acute or chronic illness, psychiatric illness, or laboratory
abnormality that, in the judgment of the investigator, may compromise the safety or
compliance of the participant, or affect the absorption of the study drug and study
assessments, or render the participant unable to complete the study.
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