Ingenol Mebutate Gel, 0.015% Repeat Use for Multiple Actinic Keratoses on Face and Scalp

Inclusion Criteria:

• Subjects must provide informed consent

• Subjects with 4 to 8 clinically typical, visible and discrete AKs within acontiguous 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 clinicalhistory of sterility (e.g. the subject is without a uterus) or,

• Childbearing potential, provided there is a confirmed negative urine pregnancytest prior to study treatment, to rule out pregnancy

• Female subjects of childbearing potential must be willing to consent to using highlyeffective 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 cellcarcinoma (SCC)

• Prior treatment with ingenol mebutate gel on face or scalp (previous treatment ontrunk and extremities acceptable)

• Selected treatment area lesions that have atypical clinical appearance

• History or evidence of skin conditions other than the trial indication that wouldinterfere with evaluation of the trial medication in the selected treatment area

• Anticipated need for hospitalization or out-patient surgery prior to Day 15 in thefirst 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 intothis 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 theClinical 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 selectedtreatment area

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