Pharmacokinetics of Ingenol Mebutate Gel in Actinic Keratosis Under Maximum Use Conditions

Inclusion Criteria:

1. Following verbal and written information about the trial, the subject must provide
informed consent documented by signing the Informed Consent Form prior to any trial-related
procedures.2. Subjects with at least 10 clinically typical, visible and discrete AKs on the
face, on approximately 250 cm2 of balding scalp or an area of approximately 250 cm2 of
sun-damaged skin on the arm except the back of the hand.

3. Subject at least 18 years of age. 4. Female subjects must be of either:

- Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history
of sterility (e.g. the subject is without a uterus) or,

- Childbearing potential, provided there is a confirmed negative urine pregnancy
test prior to trial treatment, to rule out pregnancy.

5. Female subjects of childbearing potential must be willing to use effective
contraception at trial entry and until completion. Effective contraception is
defined as follows:

- Oral/implant/injectable/transdermal/oestrogenic vaginal ring contraceptives,
intrauterine device, condom with spermicide, diaphragm with spermicide.

- Abstinence or partner's vasectomy are acceptable if the female agrees to
implement one of the other acceptable methods of birth control if her partner
changes.

Exclusion Criteria:

1. Location of the treatment area (full face, balding scalp or arm)

- within 5 cm of an incompletely healed wound,

- within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma
(SCC).

2. Prior treatment with ingenol mebutate gel within the last three months.

3. 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).

4. 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.

5. Current enrolment or participation in an investigational clinical trial within 30 days
of entry into this trial.

6. 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).

7. Subjects with QTcF interval > 450 ms for males and 470 ms for females or other
relevant pathological changes in the ECG in opinion of the investigator. These
intervals apply at Screening Visit.