Pharmacokinetics, safety, and tolerability of TQC3564, a novel CRTh2 receptor antagonist: report of the first-in-human single- and multiple-dose escalation trials in healthy Chinese subjects

ABSTRACT

Background

This is the first-in-human study to evaluate the pharmacokinetics, safety, and tolerability of TQC3564 (a novel CRTh2 receptor antagonist) in healthy Chinese subjects.

Research design and methods

This project was a phase Ia clinical study of TQC3564 as a single-ascending dose (SAD) (25 to 1200 mg) and a multiple-ascending dose (MAD) (100 or 500 mg, QD) as well as a two-period crossover food-effect study (300 mg).

Results

    In the SAD and MAD study, TQC3564 were found to be safe and well tolerated, without dose-dependent adverse events (AEs), and all AEs were mild or moderate in severity. In the SAD study, the median t_max of TQC3564 was 2.5–4.5 h, and t_1/2 was 8.13–35.7 h. Exposure was increased after food intake. The MAD study results showed that steady-state was achieved on day 4. Moreover, no apparent TQC3564 plasma accumulation was detected on day 7.

Conclusions

In healthy subjects, TQC3564 at a single dose of 25–1200 mg or 100–500 mg at multiple doses (QD) was safe and tolerable with acceptable PK profiles, indicating that TQC3564 has potential as a therapeutic option for asthma. (This study has been registered at http://www.chinadrugtrials.org.cn/ under identifier CTR20192397.)

KEYWORDS:

• TQC3564
• pharmacokinetics
• safety
• CRTh2 receptor antagonist
• asthma

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was financially supported by the Capital Construction Funds within the provincial budget in 2020 (Innovation Capacity Construction, Project #: 2020C038-1) and the National Natural Science Foundation of China (Project #: 82104314).