title: Tolerability and Pharmacokinetics of Ingenol Mebutate 0.05% Gel Applied to Treatment Areas up to 100cm(2) on the Forearm(s) of Patients with Actinic Keratosis.
abstract: OBJECTIVE
  To determine safety, tolerability, and systemic absorption of ingenol mebutate 0.05% gel applied for two consecutive days to treatment areas up to 100cm(2) on the forearm(s) of patients with actinic keratosis.
  
  
  METHODS
  Two studies are reported: a Phase 1, multicenter, open-label, dose-area escalation cohort study (http://www.clinicaltrials.gov/ct2/show/NCT00659893) and a Phase 2, double-blind, vehicle-controlled pharmacokinetic study (http://clinical trials.gov/ct2/show/NCT00852137).
  
  
  METHODS
  The Phase 1 study included male patients (n=65), mean age 68.1 years; the Phase 2 study included both male and female patients (n=16), mean age 63.3 years.
  
  
  METHODS
  In the Phase 1 study, patients assigned to escalating dose-area cohorts were evaluated for local skin responses, adverse events, and any other relevant safety data. In the pharmacokinetic study, blood samples were collected pre-dose and for up to 24 hours after administration on Day 2, and analyzed for ingenol mebutate and its primary metabolites. In both studies, safety assessments were performed on Days 2, 3, 8, 15, 29, and 57 (study end).
  
  
  RESULTS
  In the Phase 1 study, most adverse events were mild, and all treatment-related adverse events resolved before the end of the study. The 100cm(2) treatment area showed a small increase in the overall intensity of mean composite local skin response scores. There was no quantifiable systemic exposure to ingenol mebutate or its primary metabolites.
  
  
  CONCLUSIONS
  Ingenol mebutate 0.05% gel has a good safety profile when applied to treatment areas up to 100cm(2) with acceptable tolerability and local skin responses. There is no systemic absorption following application to areas of 100cm(2).
authors.affiliation: Dermatology Associates of Tyler, Texas;
authors.forename: Lawrence
authors.initials: L
authors.lastname: Anderson
authors.affiliation: DermResearch Inc., Austin, Texas;
authors.forename: Michael
authors.initials: M
authors.lastname: Jarratt
authors.affiliation: Park Avenue Dermatology, Orange Park, Florida;
authors.forename: George
authors.initials: G
authors.lastname: Schmieder
authors.affiliation: University of Sydney, Sydney, Australia;
authors.forename: Stephen
authors.initials: S
authors.lastname: Shumack
authors.affiliation: LEO Pharma Pty Ltd, Brisbane, Australia.
authors.forename: Janelle
authors.initials: J
authors.lastname: Katsamas
authors.affiliation: LEO Pharma Pty Ltd, Brisbane, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Welburn