Safety, tolerability, and pharmacokinetics of JX11502MA in Chinese healthy subjects: a first-in-human, randomized, double-blind, placebo-controlled study following single-dose administration

ABSTRACT

Background

JX11502MA is a potent partial agonist of dopamine D2 and D3 receptors, with a preferential binding profile for D3 receptors in vitro, potentially for treating schizophrenia.

Methods

A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. The subjects were randomly assigned to receive JX11502MA and placebo capsules with seven ascending dose groups: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 6 mg, and 8 mg. The PK profiles of JX11502MA and its metabolites were evaluated, along with a safety and tolerability assessment.

Results

Considering the safety of participants, the dose escalation was halted at 3 mg. Following single-dose administration, JX11502MA exhibited rapid absorption with a median T_max ranging from 1 to 1.75 h. The terminal half-life of JX11502MA ranged from 73.62 to 276.85 h. The most common treatment-emergent adverse events (TEAEs) for subjects receiving JX11502MA were somnolence (56.3%), dizziness (18.8%), nausea (21.9%), vomiting (18.8%), and hiccups (18.8%).

Conclusions

JX11502MA was generally well tolerated at a single dose of 0.25 to 3 mg. The PK profiles and safety characteristics in this study indicated that JX11502MA has the potential to be a favorable treatment option for patients with schizophrenia.

Trial registration

https://clinicaltrials.gov (identifier: NCT05233657).

KEYWORDS:

• JX11502MA
• antipsychotics
• pharmacokinetics
• schizophrenia
• safety
• tolerability

Ethics statement

The studies involving human participants were reviewed and approved by the Ethics Committee at Shanghai Mental Health Center (approval number: 2020-70C1). The participants provided their written informed consent to participate in this study.

Conflicts of interest statement

Authors J He, Y Zhou, C Bao and Z Jin are employed by Zhejiang Jingxin Pharmaceutical Co., Ltd. The authors declare that no other relevant affiliations or financial involvement with any organization or entity with financial or non-financial competing interests with the subject matter or materials discussed in the manuscript apart from those disclosed.

Data availability statement

The data that support the findings of this study are available from the corresponding author, H Li, upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2023.2291470

Acknowledgments

The authors would like to acknowledge the sponsorship and funding provided by Zhejiang Jingxin Pharmaceutical Co., Ltd, which played a role in the study’s design, conduct, data collection, management, analysis, and interpretation. The authors also express their gratitude to all the participants, study investigators, study staff, and nursing teams for their invaluable contribution to this research.

Author contribution

H Li, Y Shen and Y Zhou were responsible for the conception and design of the study. Y Yu performed the research. H Li is the principal investigator of the phase 1 study. J He, Y Li, Y Wu, C Bao and Z Jin contributed to data interpretation. J He and Z Huang drafted and revised the manuscript. Z Huang conducted the population PK analysis for the study. Y Yu, J He, Z Huang contributed equally to this work and share first authorship. All authors critically reviewed the manuscript and approved the submitted version.

Additional information

Funding

This study was supported by Zhejiang Jingxin Pharmaceutical Co., Ltd and Shanghai Clinical Research Center for Mental Health (19MC1911100).