Pharmacokinetics of ingenol mebutate gel under maximum use conditions in large treatment areas.

PURPOSE: Actinic keratoses (AKs) exist on a continuum with squamous cell carcinoma and can occur as sub-clinical and clinically visible lesions in cancerized fields on sun-damaged skin. Ingenol mebutate effectively treats AKs on areas up to 25 cm2, but actinic keratosis can affect larger areas of skin. This trial evaluated systemic exposure and safety of ingenol mebutate gel on larger areas of skin under maximum use conditions.

METHODS

Phase I, multicenter, open-label, uncontrolled, non-randomized trial. Patients received ingenol mebutate gel for three consecutive days on approximately 250 cm2 of sun-damaged skin on the full face (0.027%), the scalp (0.027%), or arm (0.06%).

RESULTS

Of 61 patients, 10 (face =8; arm =2) had ingenol mebutate in whole blood at subnanomolar levels (0.235-0.462 nM). The assayed metabolites were below the lower limit of quantification. Local skin responses increased during Days 1-4 and declined thereafter, approaching baseline by Day 16. Most adverse events were pain/pruritus of mild or moderate intensity.

CONCLUSIONS

Subnanomolar systemic exposure to ingenol mebutate was measured after application of the gel to approximately 250 cm2 on the full face, scalp, or arm under maximum use conditions. No clinically relevant systemic adverse reactions were observed, and local skin responses were manageable.