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Clin Drug Investig. 2018 Mar;38(3):249-257. doi: 10.1007/s40261-017-0608-y.

Pharmacokinetics and Safety of Ingenol Disoxate Gel Administered Under Maximum-Use Conditions to Patients With Actinic Keratosis.

Author information

1
Austin Institute for Clinical Research, 302 N Heatherwilde Boulevard #200, Pflugerville, TX, 78660, USA. ted.lain@atxderm.com.
2
LEO Pharma A/S, Ballerup, Denmark.

Abstract

BACKGROUND AND OBJECTIVES:

Ingenol disoxate (LEO 43204) is a field therapy in development for the treatment of actinic keratosis (AK) on areas between 25 and 250 cm2. We evaluated the systemic exposure and safety of ingenol disoxate under maximum-use conditions.

METHODS:

This was a phase I, open-label, non-randomized, multicenter trial. Patients ≥ 18 years of age with ≥ 15 clinically typical, visible, discrete AK lesions in a treatment area on the full face or approximately 250 cm2 on the arm or scalp were treated once-daily for 3 consecutive days with ingenol disoxate 0.018, 0.1, or 0.037% gel, respectively.

RESULTS:

The trial included 58 patients. Median age (range) of patients was 68 years (42-89) [face, N = 18], 66 years (43-88) [arm, N = 21], and 67 years (37-83) [scalp, N = 19]. The highest quantifiable ingenol disoxate level was observed in the arm group (0.33 nM, area under the concentration-time curve from time zero to the last data point [AUCtlast] 3.12 nM·h). Mean composite local skin response scores peaked at Day 4 and declined towards baseline by Day 15 in all treatment groups. Most adverse events (AEs) were of mild or moderate intensity; the most common treatment-related AEs were application-site pain (face, 88.9%; arm, 57.1%; scalp, 100.0%) and application-site pruritus (face, 50.0%; arm, 52.4%; scalp, 42.1%).

CONCLUSION:

Very low systemic exposure to ingenol disoxate was observed when applied to the face, arm, or scalp in patients with AK under maximum-use conditions. No new safety signals were identified.

TRIAL REGISTRATION:

NCT02424305.

PMID:
29204958
DOI:
10.1007/s40261-017-0608-y
[Indexed for MEDLINE]

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