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Br J Dermatol. 2017 Jun;176(6):1456-1464. doi: 10.1111/bjd.15304. Epub 2017 Apr 25.

A seamless phase I/II dose-finding trial assessing ingenol disoxate (LEO 43204) for field treatment of actinic keratosis on the scalp.

Author information

Gwinnett Clinical Research Center, Inc., Snellville, GA, U.S.A.
Collegium Medicum Berlin, Berlin, Germany.
Altman Dermatology Associates, Arlington Heights, IL, U.S.A.
LEO Pharma A/S, Ballerup, Denmark.
Laser & Skin Surgery Center Indiana, Carmel, IN, U.S.A.



Actinic keratosis (AK) is a common sun-related skin condition, which can progress to squamous cell carcinoma and occur in cancerized fields.


To investigate in a phase I/II trial the safety and efficacy of ingenol disoxate as topical field therapy for patients with AK on the balding scalp.


Part 1 was a phase I, open-label, dose-escalation trial investigating up to six doses of ingenol disoxate to determine the maximum tolerated dose (MTD). Part 2 was a phase II, randomized, double-blind, parallel group, vehicle-controlled trial. Patients were randomized 2 : 2 : 1 to receive ingenol disoxate 0·037%, 0·05% or vehicle gel once daily for two consecutive days. Percentage reduction in AK count from baseline, complete clearance (AKCLEAR 100) and partial clearance (≥ 75% AK count reduction; AKCLEAR 75) were assessed at week 8.


The MTD in part 1 was 0·075% based on a dose-dependent increase in the number and severity of adverse events. Two lower doses of ingenol disoxate gel (0·037%, 0·05%) were assessed in part 2, which showed a reduction in AK count from baseline to week 8 (0·037%, 72·7%; 0·05%, 78·5% vs. vehicle 12·6; P < 0·001), and rates of AKCLEAR 100 and AKCLEAR 75 were significantly higher in active treatment groups compared with vehicle (P ≤ 0·007). Local skin responses peaked at day 3 and declined rapidly. Adverse events were generally mild to moderate in intensity, and were most commonly application site pain/pruritus.


Ingenol disoxate 0·037% and 0·05% gel was effective and superior to vehicle, and well tolerated as field therapy for AK on the balding scalp.

[Indexed for MEDLINE]

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