Phase I, Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Safety, Tolerability, and...

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.

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.

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): T_max 4.0-5.0 h, C_max 1047.3-1730.0 ng/mL, t_1/2 10.7-18.9 h, AUC_0-∞ 17.7-42.3 µg·h/mL. In multiple-dose (steady state, 300-600 mg twice daily): T_max 2.2-3.7 h, C_max 1996.0-2880.0 ng/mL, t_1/2 9.6-17.3 h, AUC_0-∞ 46.4-78.3 µg·h/mL, AUC_ss 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.

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.