Inclusion Criteria:

- Subjects must provide informed consent

- Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous
25 cm2 treatment area on the face or scalp

- Subject at least 18 years of age

- 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 study treatment, to rule out pregnancy

- Female subjects of childbearing potential must be willing to consent to using highly
effective methods of contraception

Exclusion Criteria:

- Location of the selected treatment area:

- on any location other than the face or scalp

- on the periorbital skin

- 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 on face or scalp (previous treatment on
trunk and extremities acceptable)

- Selected treatment area lesions that have atypical clinical appearance

- History or evidence of skin conditions other than the trial indication that would
interfere with evaluation of the trial medication in the selected treatment area

- Anticipated need for hospitalization or out-patient surgery prior to Day 15 in the
first treatment cycle

- Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel

- Presence of sunburn within the selected treatment area

- Current enrollment or participation in a clinical trial within 30 days of entry into
this study

- Subjects previously entered first treatment in the trial

- Female subjects who are breastfeeding

- Subjects who are institutionalised by court order or by the local authority

- In the opinion of the investigator, the subject is unlikely to comply with the
Clinical Study Protocol

Prohibited Therapies and/or Medications within 2 weeks prior to Day 1

- Cosmetic or therapeutic procedures within 2 cm of the selected treatment area

- Use of keratolytic topical therapeutic products within 2 cm of the selected treatment
area

- Use of topical medicated creams, ointments, lotions gels, foams or sprays within 2 cm
of the selected treatment area; artificial tanners: within 5 cm of the selected
treatment area

Prohibited Therapies and/or Medications: within 4 weeks prior to Day 1

- Treatment with immunomodulators, cytotoxic drugs or interferon /interferon inducers

- Treatment with systemic medications that suppress the immune system

- Treatment/therapy with ultraviolet light A (UVA) or ultraviolet light B (UVB)

Prohibited Therapies and/or Medications within 8 weeks prior to Day 1

- Treatment with 5-fluorouracil (5-FU), imiquimod, diclofenac sodium, or photodynamic
therapy: within 2 cm of the selected treatment area

Prohibited Therapies and/or Medications within 6 months prior to Day 1

- Use of systemic retinoids or biologic/monoclonal antibody therapies