Phase I, Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Safety, Tolerability, and Pharmacokinetics of BS1801 in Healthy Chinese Adult Subjects

Guiling Chen,1, Guoping Sheng,1, Kaiqi Wu,1 Tinghan Jin,1 Qi Jiang,1 Tong Guo,1 Yifan Chen,2 Hanwei Yin,3 Guozhou Zhang,3 Zhenwei Shen,1 Huihui Zeng3 1Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310022, People’s Republic of China; 2National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, 100081, People’s Republic of China; 3Shanghai Yuanxi Medicine Corp, Shanghai, 201203, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Huihui Zeng, Email zenghh@bjmu.edu.cn Zhenwei Shen, Email shenlin7818@126.comBackground: Fibrosis is an excessive self-repair response affecting organs like the liver and lungs. Current treatments targeting local fibroblasts have significant adverse events (AEs). BS1801 is an organoselenium compound targeting thioredoxin reductase with anti-fibrotic activities. This Phase I study evaluated its safety, tolerability, and pharmacokinetics (PK) in healthy Chinese adults.Methods: This single-center, randomized, double-blind, placebo-controlled study enrolled 57 participants into single-dose (n=27) and multiple-dose (n=30) trials (placebo-to-drug ratios 1:3 and 1:4). Single doses of 450, 900, 1200, and 1800 mg were tested; multiple doses of 300, 450, and 600 mg twice daily (12± 0.5h apart) were investigated.Results: All participants completed the study. Thirty-six treatment-emergent AEs were reported, including 14 in 9 participants (20%, 95% CI: 8.3– 31.7%) in single-dose, and 22 in 11 participants (24.4%, 95% CI: 11.9– 37.0%) in multiple-dose trials. All AEs were Grade I and resolved naturally; one constipation case required medication. Using BS1801-M2 as a surrogate biomarker, PK parameters increased proportionally with single doses (450– 1800 mg): Tmax 4.0– 5.0 h, Cmax 1047.3– 1730.0 ng/mL, t1/2 10.7– 18.9 h, AUC0-∞ 17.7– 42.3 μg·h/mL. In multiple-dose (steady state, 300– 600 mg twice daily): Tmax 2.2– 3.7 h, Cmax 1996.0– 2880.0 ng/mL, t1/2 9.6– 17.3 h, AUC0-∞ 46.4– 78.3 μg·h/mL, AUCss 19.2– 28.4 μg·h/mL. Serum concentration plateaued after two doses with 45%-60% peak-to-trough fluctuation. BS1801-M2 was excreted within 96 h post-last dose.Conclusion: BS1801 is safe and well-tolerated at tested doses. Based on safety and PK profiles, the recommended dosage is 300– 450 mg twice daily. Further clinical studies are needed for evaluating the safety and efficacy of BS1801 in the target population.Keywords: phase I trial, safety, pharmacokinetics, organoselenium, thioredoxin reductase