Phase 1 Study of Topical Administration of Novel Phosphodiesterase-4 Inhibitor PF-07038124 in Japanese Healthy...

The purpose of this study was to evaluate the safety, tolerability, skin irritation potential, and pharmacokinetics of topical administration of a novel phosphodiesterase-4 inhibitor PF-07038124 in Japanese healthy adult participants. This randomized, vehicle-controlled, parallel cohort study consisted of two cohorts to evaluate participants by two administration areas in parallel: PF-07038124 at 0.01% concentration and vehicle to 2000 cm² of skin (Cohort 1) or 4000 cm² of skin (Cohort 2). Participants received repeated topical administrations of PF-07038124 or vehicle, topically applied once daily for 10 consecutive days from Day 1. In total, one mild treatment-emergent adverse event of alanine aminotransferase increase was reported and was not considered to be treatment-related. There were no changes in vital signs or in electrocardiographic data in this study. The skin irritation was reported to be score 0 using Draize scoring in all participants. The majority of concentrations on Day 10 were below the lower limit of quantification up to 24 h postdose; PF-07038124 concentrations were not measurable in 94% and 66% of plasma PK samples for the 2000 cm² and 4000 cm² treatment groups, respectively. All PF-07038124 topical doses were generally safe and well-tolerated both locally and systemically in Japanese healthy participants evaluated in this study. Trial Registration: ClinicalTrials.gov identifier: NCT04863417.