ZL-82 Double-blind Clinical Trial

NCT06432738 | Completed Phase 1

• 1 other identifier: ZL82-H-Ib
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Person

Outcome Measures

Primary Outcomes (8)

• ZL-82 Pharmacokinetics (PK)：Cmax

  security indicators

  72hours

• ZL-82 Pharmacokinetics (PK)：Tmax

  Estimation of time to reach Cmax

  72hours

• ZL-82 Pharmacokinetics (PK)：AUC0-72h

  Estimation of AUC from time zero to the last measured time point

  72hours

• ZL-82Pharmacokinetics (PK)：AUC0-∞

  Estimation of AUC from time zero extrapolated to infinity

  72hours

• ZL-82 Pharmacokinetics (PK)：MRT

  Estimation of mean residence time

  72hours

• ZL-82 Pharmacokinetics (PK)：Vd

  Estimation of apparent volume of distribution

  72hours

• ZL-82 Pharmacokinetics (PK)：t1/2

  Estimation of terminal elimination half-life

  72hours

• ZL-82 Pharmacokinetics (PK)：CLz/F

  Estimation of clearance when dosed orally

  72hours

Secondary Outcomes (3)

• Evaluation of the pharmacodynamic (PD) characteristics of single/multiple oral doses of ZL-82 tablets in healthy humans

  Day 16

• To evaluate the effect of ZL-82 tablets on QT/QTc interval in healthy subjects after single-dose administration.

  Day 16

• To evaluate the effect of ZL-82 tablets on ECG parameters (ΔQTcF/ΔΔQTcF and HR, PR, QRS intervals) in healthy subjects, as well as the effect on T wave morphology and U wave.

  Day 16

Study Arms (8)

600mg ZL-82

EXPERIMENTAL

The subjects in the single-dose group were fasted and water-free for at least 10 hours the night before the administration. On the first day of the study (D1), the subjects were given ZL-82 tablets or placebo according to the requirements of the random table, and were followed as per the study. Schedule safety inspections and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; complete a series of safety inspections, PK, and PD sample collection on the 3rd day and leave the clinical trial facility on the 7th day Safety follow-up.

Drug: ZL-82

600mg ZL-82 placebo

PLACEBO COMPARATOR

The subjects in the single-dose group were fasted and water-free for at least 10 hours the night before the administration. On the first day of the study (D1), the subjects were given ZL-82 tablets or placebo according to the requirements of the random table, and were followed as per the study. Schedule safety inspections and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; complete a series of safety inspections, PK, and PD sample collection on the 3rd day and leave the clinical trial facility on the 7th day Safety follow-up.

Drug: ZL-82 placebo

50mg ZL-82

EXPERIMENTAL

Subjects in the multiple-dose group were fasted and water-free for at least 10 hours the night before dosing, and were given ZL once a day according to the random table requirements from day 1 (D1) to day 10 (D10) of the study. -82 tablets or placebo, and undergo safety inspections according to the study schedule and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; after completing a series of safety inspections, PK, and PD sample collection on day 12 Safety follow-up was conducted on day 16 after leaving the clinical trial facility.

Drug: ZL-82

50mg ZL-82 placebo

PLACEBO COMPARATOR

Subjects in the multiple-dose group were fasted and water-free for at least 10 hours the night before dosing, and were given ZL once a day according to the random table requirements from day 1 (D1) to day 10 (D10) of the study. -82 tablets or placebo, and undergo safety inspections according to the study schedule and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; after completing a series of safety inspections, PK, and PD sample collection on day 12 Safety follow-up was conducted on day 16 after leaving the clinical trial facility.

Drug: ZL-82 placebo

100mg ZL-82

EXPERIMENTAL

Subjects in the multiple-dose group were fasted and water-free for at least 10 hours the night before dosing, and were given ZL once a day according to the random table requirements from day 1 (D1) to day 10 (D10) of the study. -82 tablets or placebo, and undergo safety inspections according to the study schedule and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; after completing a series of safety inspections, PK, and PD sample collection on day 12 Safety follow-up was conducted on day 16 after leaving the clinical trial facility.

Drug: ZL-82

100mg ZL-82 placebo

PLACEBO COMPARATOR

Subjects in the multiple-dose group were fasted and water-free for at least 10 hours the night before dosing, and were given ZL once a day according to the random table requirements from day 1 (D1) to day 10 (D10) of the study. -82 tablets or placebo, and undergo safety inspections according to the study schedule and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; after completing a series of safety inspections, PK, and PD sample collection on day 12 Safety follow-up was conducted on day 16 after leaving the clinical trial facility.

Drug: ZL-82 placebo

200mg ZL-82

EXPERIMENTAL

Subjects in the multiple-dose group were fasted and water-free for at least 10 hours the night before dosing, and were given ZL once a day according to the random table requirements from day 1 (D1) to day 10 (D10) of the study. -82 tablets or placebo, and undergo safety inspections according to the study schedule and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; after completing a series of safety inspections, PK, and PD sample collection on day 12 Safety follow-up was conducted on day 16 after leaving the clinical trial facility.

Drug: ZL-82

200mg ZL-82 placebo

PLACEBO COMPARATOR

Subjects in the multiple-dose group were fasted and water-free for at least 10 hours the night before dosing, and were given ZL once a day according to the random table requirements from day 1 (D1) to day 10 (D10) of the study. -82 tablets or placebo, and undergo safety inspections according to the study schedule and complete PK, PD, and Holter collection according to the PK, PD, and Holter collection schedule; after completing a series of safety inspections, PK, and PD sample collection on day 12 Safety follow-up was conducted on day 16 after leaving the clinical trial facility.

Drug: ZL-82 placebo

Interventions

ZL-82 DRUG

This group of subjects take ZL-82

Also known as: 600mg ZL-82, 50mg ZL-82, 100mg ZL-82, 200mg ZL-82

100mg ZL-82; 200mg ZL-82; 50mg ZL-82; 600mg ZL-82

ZL-82 placebo DRUG

This group of subjects take ZL-82 placebo

Also known as: 600mg ZL-82 placebo, 50mg ZL-82 placebo, 100mg ZL-82 placebo, 200mg ZL-82 placebo

100mg ZL-82 placebo; 200mg ZL-82 placebo; 50mg ZL-82 placebo; 600mg ZL-82 placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the trial:
• Current medical history, past medical history, and recent medication history:
• 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;
• Those with a history of dysphagia or any gastrointestinal system disease (or gastrointestinal resection, etc.) that affects drug absorption;
• Those who have donated blood within 3 months before screening, or those who plan to donate blood during this trial, or those who have had blood transfusion or blood loss ≥ 200mL within 4 weeks before the trial;
• Those who have participated in 4 or more clinical trials as subjects in the past year; or those who have participated in any clinical trials as subjects within 3 months before participating in this trial;
• Those who have a history of drug abuse within 5 years before screening or have used drugs within 3 months before screening;
• Concomitant use of strong inducers of liver metabolic enzymes (such as: omeprazole, barbiturates, carbamazepine, aminoglutethimide, griseofulvin, promethazine) within 4 weeks (28 days) before screening esters, phenytoin, gramide, rifampicin, sulfinpyrazone, roxithromycin, etc.); those who have taken any drug known to cause QT/QTc interval prolongation within 4 weeks (28 days) before screening or have Medications that pose a risk of torsade de pointes (TdP);

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Study Sites (1)

Peking University Medical Shandong Hospital of Traditional Chinese Medicine

Zibo, Shandong, 255000, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2024
• First Posted: May 29, 2024
• Study Start: March 19, 2024
• Primary Completion: August 15, 2024
• Study Completion: August 15, 2024
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)