First-in-human phase I studies of YJ001 spray applied to local skin in healthy subjects and patients with diabetic neuropathic pain

ABSTRACT

Background

The study aimed to investigate the safety, pharmacokinetics (PK), and efficacy of YJ001 spray, a candidate drug for diabetic neuropathic pain (DNP) therapy.

Research design & methods

Forty-two healthy subjects received one of four single doses (240, 480, 720, 960 mg) of YJ001 spray or placebo, and 20 patients with DNP received repeated doses (240 and 480 mg) of YJ001 spray or placebo via topical route of administration to the local skin of both feet. Safety, and efficacy assessments were performed, and blood samples were collected for PK analyses.

Results

The pharmacokinetic results revealed that the concentrations of YJ001 and its metabolites were low, and most of them were lower than the lower limit of quantitation. In patients with DNP, treatment with a 480 mg YJ001 spray dose significantly reduced pain and improved sleep quality compared with placebo. No serious adverse events (SAEs) or clinically significant findings of the safety parameters were observed.

Conclusion

Systemic exposure to YJ001 and its metabolites is low after YJ001 spray is applied locally to the skin, which will reduce systemic toxicity and adverse reactions. YJ001 appears to be well tolerated and potentially effective in the management of DNP and is a promising new remedy for DNP.

KEYWORDS:

• YJ001
• diabetic neuropathic pain (DNP)
• pharmacokinetics
• placebo
• tolerability

Acknowledgments

This study was sponsored by Zhejiang Yuejia Pharmaceuticals Co., Ltd. We thank the subjects who participating in this study, as well as all the investigators and research staff. We also thank the National Medical Products Administration of China for its supervision of this study.

Declaration of interest

Authors J. Zhang and Z. Hou were employed by Zhejiang Yuejia Pharmaceuticals Co., Ltd. J. Zhang has two patents issued by World Intellectual Property Organization, one is a bottle and a bottle cap device thereof for spray (US20210107023) and another one is a stable pharmaceutical composition containing a non-steroidal anti-inflammatory drug derivative (US20200360335). This study received funding from Zhejiang Yuejia Pharmaceuticals Co., Ltd. The funder had the following involvement with the study: study design, data collection and analysis. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Author contributions

Conception and design of the study: X. Yang, Z. Zhou, P. Fang, R. Zhu, J. Zhang, Z. Hou, and X. Fan. Project implementation: X. Yang, R. Zhu, L. Yang, X. Fan, Q. Yan, J. Li, Z. Zhou, and P. Fang. Data collection and analysis: X. Yang, R. Zhu, Z. Zhou, J. Zhang, Z. Hou, and P. Fang. Writing and/or revision of the manuscript: X. Yang, Z. Zhou, and P. Fang. All authors approved the final manuscript for submission.

Data availability statement

The data presented in this article are not readily available because of potential intellectual property.The data that support the findings of this study are available from the corresponding author upon reasonable request.

Clinical trial registration

http://www.chictr.org.cn.ChiCTR2000034147

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study received funding from Zhejiang Yuejia Pharmaceuticals Co., Ltd., and the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2020ZX09201-028).