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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

1
Gwinnett Clinical Research Center, Inc., Snellville, GA, U.S.A.
2
Collegium Medicum Berlin, Berlin, Germany.
3
Altman Dermatology Associates, Arlington Heights, IL, U.S.A.
4
LEO Pharma A/S, Ballerup, Denmark.
5
Laser & Skin Surgery Center Indiana, Carmel, IN, U.S.A.

Abstract

BACKGROUND:

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

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
28078678
DOI:
10.1111/bjd.15304
[Indexed for MEDLINE]

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