Study of Tolerability, Safety, and Pharmacokinetics of ZL-82 in Healthy Adult Subjects.
Status:
Recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
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.