Safety and Efficacy of Doses of Ingenol Mebutate Once Daily for Two or Three Consecutive Days in Subjects With Actinic Keratosis

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)