Abstract
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. 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%). 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. 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 re...Continue Reading
References
Jan 31, 2006·Journal of the European Academy of Dermatology and Venereology : JEADV·A F Kaptanoglu, L Kutluay
Dec 11, 2007·The British Journal of Dermatology·J Roewert-HuberH Kerl
Mar 16, 2012·The New England Journal of Medicine·Mark LebwohlBrian Berman
Sep 8, 2012·Clinical, Cosmetic and Investigational Dermatology·Brian Berman
Dec 19, 2012·Journal of the American Academy of Dermatology·Darrell S Rigel, Linda F Stein Gold
Dec 19, 2012·Journal of the American Academy of Dermatology·Roger I Ceilley, Joseph L Jorizzo
Dec 13, 2012·Drugs·Gillian M Keating
Jan 25, 2013·Clinical Interventions in Aging·Elizabeth E Uhlenhake
May 8, 2013·The British Journal of Dermatology·R N WernerA Nast
Jun 20, 2013·Clinical and Experimental Dermatology·E Campalani, C A Holden
Jul 31, 2014·Dermatology and Therapy·Robert RosenJanelle Katsamas
Sep 16, 2015·Journal of the European Academy of Dermatology and Venereology : JEADV·R N WernerUNKNOWN European Dermatology Forum
Jun 21, 2016·Histopathology·Johan SelmerDavid Weedon
Aug 20, 2016·British Journal of Sports Medicine·Nicky van MelickMaria W G Nijhuis-van der Sanden
Citations
Aug 4, 2018·Expert Opinion on Drug Metabolism & Toxicology·Eggert Stockfleth, Mike Bastian
Mar 30, 2020·The British Journal of Dermatology·L D CrowS T Arron
Dec 6, 2017·Clinical Drug Investigation·Edward LainAnders Hall
Apr 10, 2021·Expert Opinion on Drug Safety·Elias A T KochMarkus V Heppt
May 1, 2021·Cells·Uly SumarniJürgen Eberle