ZL-82 tablets are highly selective covalent irreversible inhibitors of non-receptor tyrosine protein kinase 3 (Janus kinase 3, JAK3) developed by Chengdu Zenitar Biomedical Technology Co., Ltd. According to Document No. 44 of 2020 "Chemical Drug Registration Classification and Application Document Requirements", it belongs to Category 1 chemical drugs and is an innovative drug that has not been marketed at home or abroad.
ZL-82 tablets have completed non-clinical pharmacology, non-clinical PK, and toxicology experiments, and have obtained the first-in-human randomized double-blind, placebo-controlled, dose-increasing dose-increasing approval for single oral administration of ZL-82 tablets. Partial results of the phase I clinical study on safety tolerability, pharmacokinetics and preliminary pharmacodynamics. It is necessary to further explore the safety, tolerability, pharmacokinetics and pharmacodynamic characteristics of multiple administrations based on the results obtained from the first human trial.
Non-clinical in vitro hERG tests and in vivo animal safety pharmacology tests of ZL-82 tablets showed no relevant cardiac safety concerns. According to the ICH E14 guideline "Clinical Evaluation of QT/QTc Interval Prolongation and Potential Proarrhythmic Effects of Non-Antiarrhythmic Drugs" Evaluation》2, it is recommended to conduct cardiac safety evaluation of experimental drugs with systemic bioavailability to evaluate the impact of experimental drugs on cardiac safety. This evaluation should include evaluation of the effect of the new drug on the QT/QTc interval and collection of adverse cardiovascular events. Establishing a relationship between ZL-82 drug concentration and QT/QTc interval changes will provide additional information for the analysis of cardiac repolarization trial planning and interpretation to facilitate analysis of the effects of drugs on QT/QTc interval changes. Concentration-response analysis, used to characterize the effect of the test drug on the QT/QTc interval, can be used as an alternative to time point analysis.
This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic characteristics of ZL-82 tablets in single/multiple oral doses in healthy subjects, and will also evaluate the effect of ZL-82 tablets on QTc.
Who can participate
Age range18 Years – 50 Years
SexALL
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Inclusion criteria
✓. Those who can understand the informed consent form, voluntarily participate in the trial and sign the informed consent form.
✓. Male or female; aged between 18 and 50 years old (including 18 and 50 years old).
✓. Male subjects weigh \>=50kg, female subjects weigh \>=45kg, body mass index (BMI) between 19.0\~26.0kg/m\^2, BMI = weight (kg)/height\^ 2 (m\^2), including boundary values.
✓. The subject can communicate well with the researcher and complete the trial in compliance with the requirements of the protocol.
Exclusion criteria
✕. Those who have a history of severe systemic diseases (including cardiovascular system, digestive system, urinary system, respiratory system, etc.), mental illness, and drug dependence;
✕. Have a history of structural heart disease, heart failure, myocardial infarction, angina pectoris, torsade de pointes, ventricular tachycardia, QT prolongation syndrome or symptoms of QT prolongation syndrome (such as syncope) , convulsions) and family history (proven hereditary or close relatives died suddenly due to cardiac causes when young);
. Physical examination, vital signs, laboratory examination items and test-related examinations and tests during the screening period or baseline period (for example: chest X-ray examination, abdominal color ultrasound, blood pregnancy test, ANA examination, gamma-interferon release Test, 12-lead electrocardiogram, etc.) with abnormal results and clinical significance;
✕. Patients with a history of lipid metabolism defects, such as: familial hyperlipidemia, lipoid nephropathy, or patients with acute pancreatitis accompanied by hyperlipidemia;
✕. Nervous/psychiatric, respiratory system, cardiovascular system, digestive tract system, blood and lymphatic system, endocrine system, musculoskeletal system diseases, liver and kidney dysfunction, or any other diseases and physiological conditions that may affect the test results during screening By;
✕. Those with allergies, or those with a history of food or drug allergies or other allergic diseases (asthma, urticaria, eczematous dermatitis, etc.) that are clinically significant as determined by the researcher; or those who are known to be allergic to JAK inhibitors or to the test Those who are allergic to the excipients contained in the medicine;
✕. Those who have suffered from clinically significant diseases or undergone major surgeries within 3 months before screening;
✕. Those who suffered from acute diseases within 2 weeks before screening; those who had clinically significant infections within 3 months before screening (such as upper respiratory tract infection, nasopharyngitis, urinary tract infection, etc.); those who had any evidence of infection within 7 days before screening (such as Fever, cough, sputum, headache, etc.); those with a history of herpes simplex infection or recurrent (\>1 time) herpes zoster or disseminated herpes zoster;