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