Phase I Clinical Study of ZL-82 Tablets

NCT ID: NCT06055023

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-09
• Study Completion Date: 2024-06-13

Brief Summary

ZL-82 is an oral janus kinase (JAK) inhibitor. In vitro biological mass spectrometry identification test proves that ZL-82 can selectively and irreversibly inhibit JAK3. It has obvious safety advantages, with a wide therapeutic window and controllable cardiotoxicity. This is also demonstrated from preliminary GLP-conditions of acute toxicity in SD rats and Beagle dogs. Results of 4-week long-term toxicity in Beagle dogs also support this notion. Therefore, ZL-82 has the potential to treat rheumatoid arthritis. It Used to relieve and heal swelling, pain, stiffness, and limited mobility that may be caused by rheumatoid arthritis.The drug is intended to be used in patients with RA to relieve and heal swelling, pain, stiffness, and limited mobility that may be caused by rheumatoid arthritis.

Pharmacodynamic studies show that ZL-82 has a strong inhibitory effect on JAK3 with IC50 of 2.8 nM, and has no obvious inhibitory effect on JAK1, JAK2 and TYK2. Compared with the similar drug Tofacitinib, its inhibitory effect on JAK3 subtype is 1nM, but its inhibition IC50 for JAK1 subtype and JAK2 subtype are 112nM and 20nM, respectively.and its selectivity is 100-fold and 20-fold, respectively.Also, the selectivity multiples of ZL-82 were 100-fold and 20-fold than tofacitinib , respectively, which indicates that ZL-82 is more selective than the marketed Tofacitinib.This allows ZL-82 to precisely inhibit JAK kinase and block a series of cytokines in the downstream signaling pathway. And show significant effect on rheumatoid arthritis.

The experimental results showed that in DTH and CIA models, 25, 50, 75, and 100 mg/kg of this variety could dose-dependently inhibit joint swelling in mice.

Objectives of Study

Main Purpose:

1. To evaluate the tolerability, safety and pharmacokinetic characteristics of a single oral dose of ZL-82 tablets in healthy adult subjects;

2. To explore the effect of eating on the PK of oral ZL-82 tablets in healthy adult subjects;

3. To evaluate the tolerability, safety and pharmacokinetics of ZL-82 tablets after multiple oral administration in healthy adult subjects.

Conditions

Rheumatoid Arthritis (RA); Inflammatory Bowel Disease - IBD1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

ZL-82

1 case，The starting dose，Take the medicine once on D1 ，D1 through 7.

Group Type: EXPERIMENTAL

ZL-82 12.5mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 25mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 50mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 100mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 200mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 300mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 450mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 600mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

zL-82 placebo group

1 case,The starting dose,Take the medicine once on D1,D1-7.

Group Type: PLACEBO_COMPARATOR

zL-82 placebo 12.5mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 placebo 25mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 placebo 50mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 placebo 100mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 placebo 200mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 placebo 300mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7. Edit

ZL-82 placebo 450mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

ZL-82 placebo 600mg

Intervention Type: DRUG

1 case,The starting dose,Take the medicine once on D1,D1-7.

Interventions

ZL-82 12.5mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 25mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 50mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 100mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 200mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 300mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 450mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 600mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

zL-82 placebo 12.5mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 placebo 25mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 placebo 50mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 placebo 100mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 placebo 200mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 placebo 300mg

1 case,The starting dose,Take the medicine once on D1,D1-7. Edit

Intervention Type: DRUG

ZL-82 placebo 450mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

ZL-82 placebo 600mg

1 case,The starting dose,Take the medicine once on D1,D1-7.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy subjects, regardless of gender, 18 to 45 years old (including 18 and 45 years old)
• The weighing of male subjects ≥ 50kg, female subjects ≥ 45kg, and a body mass index (BMI) between 19 and 25kg/m2 (including boundary values)
• The medical history, physical examination, laboratory examination items and various tests and tests related to the trial before enrollment were normal or abnormal without clinical significance, and the clinical research doctor judged that they were qualified.
• Be able to understand the informed consent form, voluntarily participate in the trial and sign the informed consent form

Exclusion Criteria

• Allergic constitution, such as those who are known to be allergic to two or more substances, or those who are known to be allergic to JAK inhibitors or to the excipients contained in the test drug
• ALT and/or AST>1×ULN, TIB>1×ULN, GGT>1×ULN; Scr>1×ULN
• Major surgery within the 3 months prior to the trial or planning to undergo surgery during the trial
• Acute illness within 2 weeks prior to trial
• Have any serious diseases such as cardiovascular system, digestive system, urinary system, respiratory system, nervous system, immune system, endocrine system, malignant tumor, mental illness, etc.
• History of dysphagia or any gastrointestinal disease (or gastrointestinal resection, etc.) affecting drug absorption
• HIV antibody, Treponema pallidum antibody, hepatitis B surface antigen and hepatitis C antibody test are positive
• Positive urine drug screen (including morphine, methamphetamine, ketamine, MDMA, THC)
• Systolic blood pressure>140mmHg or diastolic blood pressure>90mmHg during the screening period;
• Blood donation or blood loss ≥400mL within 3 months, or blood transfusion; blood donation or blood loss ≥200mL within 1 month;
• Have special requirements for diet or cannot comply with the unified diet and corresponding regulations of the research center
• Alcoholics (alcoholism refers to drinking 60-degree white wine ≥10.5L or red wine ≥3.5L per week for more than 5 years), drinking a lot of coffee-containing beverages (more than 8 cups per day, 1 cup = 250ml) or heavy smoking (average > 20 sticks/day);
• Have used any prescription drugs (JAK inhibitors, etc.) that may have an effect on the test drug within 2 weeks;
• 4 weeks (28 days) before enrollment, strong inducers of liver metabolic enzymes was limit. ( such as omeprazole, barbiturates, carbamazepine, aminoglutamine, griseofulvin, carbamazepine, Phenytoin, Gluter, Rifampicin, Sulfinpyrazone, Roxithromycin, etc. )
• Participate in clinical trials of other drugs or medical devices as subjects within 3 months
• Women who are pregnant or breastfeeding or women of childbearing age who have had unprotected sex with their partner within 14 days before the test;
• The subjects or their partners are unwilling to use non-drug contraceptive measures (such as total abstinence, condoms, IUDs, ligation, etc.) for contraception during the trial, or the subject and his partner has a pregnancy plan within 6 months of signing the informed consent;
• Not suitable to participate in the trial according to the judgment of the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chengdu Zenitar Biomedical Technology Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chen Lijuan, doctor

Role: STUDY_CHAIR

West China Hospital

Locations

Affiliated Hospital of Guizhou Medical University

Guizhou, GuiYang, China

Countries

China

Other Identifiers

H-ZL82-PI-I

Identifier Type: -

Identifier Source: org_study_id