Phase I Clinical Study of ZL-82 Tablets

NCT06055023 | Completed Phase 1 DMC

• 1 other identifier: H-ZL82-PI-I
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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. 1.To evaluate the tolerability, safety and pharmacokinetic characteristics of a single oral dose of ZL-82 tablets in healthy adult subjects;
2. 2.To explore the effect of eating on the PK of oral ZL-82 tablets in healthy adult subjects;
3. 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

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetics (PK) of ZL-82：Cmax

  Estimation of maximum observed plasma concentration

  24hours

• Pharmacokinetics (PK) of ZL-82：Tmax

  Estimation of time to reach Cmax

  24hours

• Pharmacokinetics (PK) of ZL-82：AUC0-24h

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

  24hours

• Pharmacokinetics (PK) of ZL-82：AUC0-∞

  Estimation of AUC from time zero extrapolated to infinity

  24hours

• Pharmacokinetics (PK) of ZL-82：Vd

  Estimation of apparent volume of distribution

  24hours

• Pharmacokinetics (PK) of ZL-82：t1/2

  Estimation of terminal elimination half-life

  24hours

• Pharmacokinetics (PK) of ZL-82：CLz/F

  Estimation of clearance when dosed orally

  24hours

• Pharmacokinetics (PK) of ZL-82：Vz/F

  Estimation of apparent volume of distribution when dosed orally

  24hours

• Pharmacokinetics (PK) of ZL-82：Kel

  Estimation of the elimination rate constant of a drug in the body

  24hours

Study Arms (2)

ZL-82

EXPERIMENTAL

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

Drug: ZL-82 12.5mg; Drug: ZL-82 25mg; Drug: ZL-82 50mg; Drug: ZL-82 100mg; Drug: ZL-82 200mg; Drug: ZL-82 300mg; Drug: ZL-82 450mg; Drug: ZL-82 600mg

zL-82 placebo group

PLACEBO COMPARATOR

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

Drug: zL-82 placebo 12.5mg; Drug: ZL-82 placebo 25mg; Drug: ZL-82 placebo 50mg; Drug: ZL-82 placebo 100mg; Drug: ZL-82 placebo 200mg; Drug: ZL-82 placebo 300mg; Drug: ZL-82 placebo 450mg; Drug: ZL-82 placebo 600mg

Interventions

ZL-82 12.5mg DRUG

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

ZL-82

ZL-82 25mg DRUG

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

ZL-82

ZL-82 50mg DRUG

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

ZL-82

ZL-82 100mg DRUG

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

ZL-82

ZL-82 200mg DRUG

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

ZL-82

ZL-82 300mg DRUG

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

ZL-82

ZL-82 450mg DRUG

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

ZL-82

ZL-82 600mg DRUG

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

ZL-82

zL-82 placebo 12.5mg DRUG

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

zL-82 placebo group

ZL-82 placebo 25mg DRUG

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

zL-82 placebo group

ZL-82 placebo 50mg DRUG

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

zL-82 placebo group

ZL-82 placebo 100mg DRUG

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

zL-82 placebo group

ZL-82 placebo 200mg DRUG

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

zL-82 placebo group

ZL-82 placebo 300mg DRUG

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

zL-82 placebo group

ZL-82 placebo 450mg DRUG

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

zL-82 placebo group

ZL-82 placebo 600mg DRUG

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

zL-82 placebo group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd: lead

Study Sites (1)

Affiliated Hospital of Guizhou Medical University

Guizhou, GuiYang, China

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Crohn Disease

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Chen Lijuan, doctor

  West China Hospital

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: September 26, 2023
• Study Start: April 9, 2023
• Primary Completion: January 28, 2024
• Study Completion: June 13, 2024
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)