A Phase I Study to Evaluate the Safety and Pharmacokinetics of SHR0302 Base Ointment in Healthy Adult Volunteers.

IF 2.8 4区医学 Q2 DERMATOLOGY

Skin Pharmacology and Physiology Pub Date : 2023-01-01 DOI:10.1159/000528739

Baoping Li, Nanyang Li, Aik Han Goh, Haifeng Cao, Min Wang Irwin, Xunian Tong, Jingjing Wang, Xiaojie Wu, Jing Zhang, Dan Pu

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引用次数: 0

Abstract

Introduction: SHR0302 is a highly selective JAK1 inhibitor. This study aimed to investigate the safety, tolerability, and pharmacokinetics of single and multiple-dose topical skin application of SHR0302 base ointment in healthy adult subjects.

Methods: This phase I clinical trial (registration number: CTR20192188) consisted of two parts. Part 1 was a single-dose ascending study with four dose levels in 32 healthy Australian adults (8 subjects in each dose group). All Australian subjects were randomized 3:1 to a single-dose topical skin application of SHR0302 base ointment or placebo. The dose escalated from 1% SHR0302 base ointment on 3% of body surface area (BSA) to 2% SHR0302 base ointment on 20% of BSA. Part 2 combined single and multiple-dose ascension studies with two dose levels in 20 healthy Chinese adults (10 subjects in each dose group). All Chinese subjects were randomized 4:1 to a combination of single and multiple doses for consecutive 10 days of topical application of 1% SHR0302 base ointment on 20% BSA or 2% SHR0302 base ointment on 20% BSA. The safety and pharmacokinetics of the SHR0302 base ointment were evaluated.

Results: The incidence of treatment-emergent adverse events (TEAEs) in both parts was comparable between the SHR0302 base ointment group and the vehicle group (part 1: 33.3% vs. 37.5%; part 2: 56.3% vs. 75.0%). All TEAEs were transient, recovered, and equally well-tolerated in the two racial groups. The overall absorption of the SHR0302 base ointment was slow after topical application, with Tmax>10 h. After a single dose of the SHR0302 base ointment, drug exposure in healthy Australian and Chinese subjects increased nonlinearly with the increase in the administration area and drug content. Drug exposure increased in a less-than-dose-proportional manner within the dose range tested. Due to differences in the clinical practice of topical application, the Tmax of the drug in Australian subjects was earlier than in Chinese subjects, but the overall extent of absorption seemed comparable in Australian and Chinese subjects (with comparable AUC0-t).

Conclusion: The SHR0302 base ointment (either single or multiple doses) was well tolerated and safe, with no racial disparity.

Key message: The SHR0302 base ointment (either single or multiples doses) was well tolerated and safe.

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SHR0302基础软膏在健康成人志愿者中的安全性和药代动力学的I期研究

SHR0302是一种高选择性JAK1抑制剂。本研究旨在探讨健康成人单次和多次皮肤外用SHR0302基础软膏的安全性、耐受性和药代动力学。方法:该I期临床试验(注册号:CTR20192188)由两部分组成。第一部分是单剂量上升研究，在32名健康的澳大利亚成年人中有4个剂量水平(每个剂量组8名受试者)。所有澳大利亚受试者按3:1随机分为单剂量局部皮肤涂抹SHR0302基础软膏或安慰剂。剂量从1% SHR0302基础软膏覆盖3%的体表面积(BSA)增加到2% SHR0302基础软膏覆盖20%的BSA。第二部分对20名健康中国成人进行单剂量和多剂量提升联合研究，两种剂量水平(每组10名受试者)。所有中国受试者按4:1随机分为单剂量和多剂量组合，连续10天局部应用1% SHR0302基础软膏涂抹20% BSA或2% SHR0302基础软膏涂抹20% BSA。对SHR0302软膏的安全性和药代动力学进行了评价。结果:SHR0302基础软膏组和载药组治疗后出现的不良事件(teae)的发生率在第一部分:33.3% vs. 37.5%;第二部分:56.3% vs. 75.0%)。所有的teae都是短暂的，恢复的，并且在两个种族群体中同样具有良好的耐受性。外用SHR0302基础软膏后，整体吸收缓慢，Tmax>10 h。单剂量SHR0302基础软膏后，澳大利亚和中国健康受试者的药物暴露量随给药面积和药物含量的增加呈非线性增加。在测试的剂量范围内，药物暴露以低于剂量比例的方式增加。由于外用临床实践的差异，澳大利亚受试者的Tmax比中国受试者早，但澳大利亚和中国受试者的整体吸收程度似乎相当(AUC0-t相当)。结论:SHR0302基础软膏(单剂或多剂)耐受性良好且安全，没有种族差异。关键信息:SHR0302基础软膏(单剂量或多剂量)耐受性良好且安全。

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来源期刊

Skin Pharmacology and Physiology 医学-皮肤病学

CiteScore

5.20

自引率

7.40%

发文量

审稿时长

>12 weeks

期刊介绍： In the past decade research into skin pharmacology has rapidly developed with new and promising drugs and therapeutic concepts being introduced regularly. Recently, the use of nanoparticles for drug delivery in dermatology and cosmetology has become a topic of intensive research, yielding remarkable and in part surprising results. Another topic of current research is the use of tissue tolerable plasma in wound treatment. Stimulating not only wound healing processes but also the penetration of topically applied substances into the skin, this novel technique is expected to deliver very interesting results.