Pharmacokinetics, Safety, and Tolerability of a Single 5‐Day Treatment of Tirbanibulin Ointment 1% in 100 cm2: A Phase 1 Maximal‐Use Trial in Patients with Actinic Keratosis

Abstract Tirbanibulin ointment 1% is approved in the United States and Europe for the treatment of actinic keratosis with demonstrated efficacy, safety, and tolerability when applied over a field up to 25 cm 2 . This Phase 1 maximal‐use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100 cm 2 of the face or balding scalp in adults with actinic keratosis. Twenty‐eight patients self‐applied tirbanibulin once daily for a single 5‐day treatment course. On Day 5, the mean maximum plasma concentration was 1.06 ng/mL and area under the plasma concentration‐time curve during a dosing interval was 16.2 ng • h/mL. Systemic exposure was approximately 4‐fold higher than in a previous pharmacokinetic study with a 25 cm 2 field, consistent with the increase in the treated area. Tirbanibulin applied to a 100‐cm 2 treatment field showed favorable safety and tolerability. The most common treatment‐emergent adverse events were application site reactions (in 35.7% of patients). All treatment‐emergent adverse events and most of the tolerability signs were mild/moderate and resolved or returned to baseline by Day 29. In summary, under maximal‐use conditions, tirbanibulin ointment 1% was safe and well tolerated supporting its potential use over a field up to 100 cm 2 .