Thaçi Diamant, Gooderham Melinda, Lovato Paola, Madsen Daniel Elenius, Soehoel Anders, Bissonnette Robert
Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany.
Department of Dermatology, Queens University, Peterborough, Ontario, Canada.
J Eur Acad Dermatol Venereol. 2025 Sep;39(9):1612-1621. doi: 10.1111/jdv.20777. Epub 2025 Jun 17.
Chronic Hand Eczema (CHE) is a prevalent inflammatory skin condition characterized by pain, pruritus and significant impact on patients' quality of life. Delgocitinib cream, a pan-Janus kinase inhibitor, has shown potential in targeting the key mediators of CHE. To develop a detailed trial drug safety profile, it is vital to assess systemic exposure and bioavailability following repeated drug applications.
This analysis aimed to evaluate the systemic exposure and bioavailability of delgocitinib cream 20 mg/g in adults with moderate to severe CHE and compare these parameters with those from oral delgocitinib administration in healthy adults.
An open-label, single-arm, Phase 1 trial (NCT05486117) was conducted involving 16 adults with moderate to severe CHE. Participants applied delgocitinib cream 20 mg/g twice daily for 1 week. Pharmacokinetic sampling was performed on Day (D)1 and D8. Systemic exposure was compared with data from two Phase 1 trials involving oral delgocitinib in healthy adults (1.5-12 mg, NCT05050279, and 1-100 mg, NBX1-1).
Delgocitinib cream demonstrated minimal systemic exposure, with geometric mean maximum plasma concentration (C) values of 0.50 ng/mL on D1 and 0.46 ng/mL on D8. The geometric mean area under the concentration-time curve from 0 to 12 h (AUC) was 2.5 hng/mL on D1 and 3.7 hng/mL on D8. No significant accumulation of delgocitinib was observed over time. Systemic exposure with topical application was significantly lower than with oral administration, with a relative bioavailability of 0.6%. Delgocitinib cream was well tolerated, with no reported adverse events during the trial.
Delgocitinib cream shows minimal systemic exposure and is well tolerated in patients with moderate to severe CHE. These findings suggest that no systemic pharmacological effect is expected with the application of delgocitinib cream 20 mg/g to the hands and wrists of patients with moderate to severe CHE.
gov (or equivalent) listing: NCT05486117, NCT05050279.
慢性手部湿疹（CHE）是一种常见的炎症性皮肤病，其特征为疼痛、瘙痒，对患者生活质量有重大影响。泛JAK激酶抑制剂地尔戈替尼乳膏已显示出针对CHE关键介质的潜力。为了制定详细的试验药物安全性概况，评估重复用药后的全身暴露和生物利用度至关重要。
本分析旨在评估20mg/g地尔戈替尼乳膏在中度至重度CHE成人患者中的全身暴露和生物利用度，并将这些参数与健康成人口服地尔戈替尼的参数进行比较。
进行了一项开放标签、单臂1期试验（NCT05486117），纳入16例中度至重度CHE成人患者。参与者每天两次涂抹20mg/g地尔戈替尼乳膏，持续1周。在第1天（D1）和第8天（D8）进行药代动力学采样。将全身暴露情况与两项涉及健康成人口服地尔戈替尼的1期试验（1.5 - 12mg，NCT05050279，以及1 - 100mg，NBX1 - 1）的数据进行比较。
地尔戈替尼乳膏显示出最小的全身暴露，D1时几何平均最大血浆浓度（Cmax）值为0.50ng/mL，D8时为0.46ng/mL。0至12小时浓度 - 时间曲线下的几何平均面积（AUC）在D1时为2.5hng/mL，D8时为3.7hng/mL。未观察到地尔戈替尼随时间有明显蓄积。局部应用的全身暴露显著低于口服给药，相对生物利用度为0.6%。地尔戈替尼乳膏耐受性良好，试验期间未报告不良事件。
地尔戈替尼乳膏全身暴露最小，在中度至重度CHE患者中耐受性良好。这些发现表明，对中度至重度CHE患者的手部和腕部涂抹20mg/g地尔戈替尼乳膏预计不会产生全身药理作用。
gov（或同等机构）登记号：NCT05486117，NCT05050279。
