Phase 1 Maximal Use Pharmacokinetic Study of Tirbanibulin Ointment 1% in Subjects With Actinic Keratosis

Abstract Tirbanibulin is a novel tubulin polymerization and Src kinase signaling inhibitor. This study was designed to fully characterize tirbanibulin pharmacokinetics (PK) when applied topically under maximal use conditions. This was an open‐label, parallel‐group PK safety study of tirbanibulin ointment 1% applied to 25 cm 2 of the face or balding scalp in adults with actinic keratosis (AK). Eligible subjects self‐applied tirbanibulin once‐daily for 5 days. PK sampling occurred on days 1, 3 and 4 at 0 hour (before dosing), and on day 5 at prespecified time points up to 24 hours after application. Safety assessments included adverse events and local skin reactions were evaluated up to day 29. Eighteen subjects (face or scalp, n = 9 each) completed the study. Subjects were White (100%), of mean [range] age 66.4 [43‐83] years, predominantly men (83.3%) with Fitzpatrick skin type I to III (94.4%); baseline AK lesion count, mean [range] 8.2 [6‒14]. All subjects had quantifiable but low plasma concentrations of tirbanibulin. On day 5, overall mean (standard deviation) maximum concentration (C max ) was 0.26 (0.23) ng/mL (or 0.60 nM), median time to maximum concentration was 6.91 hours, and mean (standard deviation) area under the plasma concentration–time curve from time 0 to 24 hours was 4.09 (3.15) ng ∙ h/mL. Four subjects experienced a total of 5 treatment‐emergent adverse events that resolved. Mild to moderate erythema, flaking, or scaling in the treatment area peaked around day 8 before resolving or returning to baseline by day 29. In conclusion, under maximal use conditions, tirbanibulin ointment 1% for 5 days in the treatment of AK on the face or scalp was well tolerated and resulted in low systemic exposure with subnanomolar plasma concentrations.