Systemic exposure and bioavailability of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema.

BACKGROUND

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.

OBJECTIVES

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

CLINICALTRIALS

gov (or equivalent) listing: NCT05486117, NCT05050279.