Safety, tolerability, and pharmacokinetics of HL-300, a novel topical pan-JAK inhibitor, in healthy Chinese adults: a first-in-human, randomized, double-blind, placebo-controlled phase I trial.

Abstract

Introduction: HL-300 is a novel topical pan-JAK inhibitor targeting JAK1, JAK2, JAK3, and TYK2 for atopic dermatitis (AD). This first-in-human study evaluated its safety, tolerability, and pharmacokinetics (PK) in healthy Chinese adults.

Methods: In a randomized, double-blind, placebo-controlled phase I trial, 36 subjects received single or multiple topical doses of HL-300 (0.25%, 0.5%, or 1.0%) or placebo. Safety and PK parameters were assessed.

Results: Following single dosing, HL-300 showed slow absorption, with mean Cmax ranging from 82.77 to 537.60 pg/mL and median Tmax of 24-36 h. After multiple dosing, steady state was reached by Day 6, with a Cmax,ss of 3059 pg/mL. Accumulation ratios for AUC and Cmax were 40.93 and 18.9, respectively. Most treatment-emergent adverse events were mild (Grade 1), and no serious adverse events were reported.    .

Conclusion: HL-300 was generally safe and well tolerated after single and multiple topical administrations, showing low systemic exposure after single dosing and predictable PK with steady-state attainment after repeated dosing. These findings support further clinical development and dose optimization in patients with AD.