A dose-finding trial with a novel ingenol derivative (ingenol disoxate: LEO 43204) for field treatment of actinic keratosis on full face or 250 cm² on the chest

Purpose: Actinic keratoses (AKs) may progress to squamous cell carcinoma and can occur in cancerized fields as sub-clinical and clinically visible lesions. Ingenol disoxate gel is a topical field therapy for AK. This Phase I/II trial aimed to assess the safety and efficacy of ingenol disoxate on full face or chest in patients with AKs. Materials and methods: Part 1 was a phase-I, open-label, dose-escalation trial investigating the maximum tolerated dose of ingenol disoxate. Part 2 was a phase-II, randomized, double-blind, vehicle-controlled trial; patients were randomized 1:1:1:1 to ingenol disoxate 0.018%, 0.012%, 0.006% gel or vehicle for 2 consecutive days. Results: Reduction in AK count from baseline at Week 8 was significantly higher than with vehicle for all doses of ingenol disoxate gel (0.018%, 79.0%; 0.012%, 73.4%; 0.006%, 69.7%; vehicle; 42.3%; p <.001). Local skin responses peaked at Day 3 for all doses, rapidly declined, and reached mild levels at Week 2. Most adverse events were mild or moderate in intensity, and were most commonly application site pain/pruritus. Conclusions: Ingenol disoxate gel is efficacious and well tolerated as field treatment for AKs on the full face or chest. Clinical Trial No.: NCT01922050.