Phase I Clinical Study of ZL-82 Tablets

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

Interventions

DRUG

ZL-82 12.5mg

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

DRUG

ZL-82 25mg

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

DRUG

ZL-82 50mg

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

DRUG

ZL-82 100mg

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

DRUG

ZL-82 200mg

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

DRUG

ZL-82 300mg

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

DRUG

ZL-82 450mg

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

DRUG

ZL-82 600mg

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

DRUG

zL-82 placebo 12.5mg

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

DRUG

ZL-82 placebo 25mg

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

DRUG

ZL-82 placebo 50mg

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

DRUG

ZL-82 placebo 100mg

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

DRUG

ZL-82 placebo 200mg

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

DRUG

ZL-82 placebo 300mg

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

DRUG

ZL-82 placebo 450mg

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

DRUG

ZL-82 placebo 600mg

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

Sponsors & Collaborators

• Chengdu Zenitar Biomedical Technology Co., Ltd

  lead INDUSTRY

Principal Investigators

• Chen Lijuan, doctor · West China Hospital

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-04-09

Primary Completion

2024-01-28

Completion

2024-06-13

Countries

• China

Study Locations