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

• Published in: Clinical drug investigation 2018-03, Vol.38 (3), p.249-257
• Main Authors: Lain, Edward, Skov, Torsten, Hall, Anders
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Diterpenes - administration & dosage; Diterpenes - adverse effects; Diterpenes - blood; Diterpenes - pharmacokinetics; Female; Gels; Humans; Internal Medicine; Keratosis, Actinic - blood; Keratosis, Actinic - diagnosis; Keratosis, Actinic - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; NCT; NCT02424305; Original Research Article; Pain - blood; Pain - chemically induced; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Pruritus; Pruritus - blood; Pruritus - chemically induced; Skin; Transdermal medication; Treatment Outcome; Ultraviolet radiation
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-017-0608-y

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 cm 2 . 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 cm 2 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 [AUC tlast ] 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.