Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis

To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel


Eligibility Criteria:
Inclusion Criteria:

* Subjects must be competent to understand the nature of the trial and provide informed consent
* Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face, the balding scalp (the balding part of the scalp should be at least 25 cm2) or a contiguous area of approximately 250 cm2 on the chest
* Subject at least 18 years of age
* Female subjects must be of either:

  1. Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,
  2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy
* Female subjects of childbearing potential1 must be willing to use effective contraception at trial entry and until completion

Exclusion Criteria:

* Location of the treatment area (full face, full balding scalp or chest)

  * within 5 cm of an incompletely healed wound,
  * within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC
* Prior treatment with ingenol mebutate gel within the treatment area
* Lesions in the treatment areas that have:

  * atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or,
  * recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions
* History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
* Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
* Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety and efficacy during the course of the trial, as determined by the investigator's clinical judgment
* Any abnormal laboratory tests that are medically significant and would impact the safety of the subjects or the interpretation of the trial results, as determined by the investigator's judgment
* Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications
* Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
* Presence of acute sunburn within the treatment areas
* Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.
* Subjects previously assigned to treatment in Part 1 or rand
* Female subjects who are breastfeeding.
* In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state)