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 cm² . This Phase 1 maximal-use trial determines the plasma pharmacokinetics, safety, and tolerability of tirbanibulin ointment 1% applied to 100 cm² 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 cm² field, consistent with the increase in the treated area. Tirbanibulin applied to a 100-cm² 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 cm² .

Keywords: actinic keratosis; maximal-use; safety; tirbanibulin; topical pharmacokinetics.