PEP005 Gel - Biological Effects in Actinic Keratosis Assessed by Histology

• Leukocytes Infiltration normal Skin [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Degree of skin infiltration of leukocytes in haematoxylin & eosin-stained sections assessed on a scale from 0 to 3 in the normal skin biopsies from day 3 compared to baseline and to AK lesion biopsies
• Necrosis normal Skin [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Degree of necrosis of the epidermis and dermis in haematoxylin & eosin-stained sections assessed as binary outcome (present/absent) in the normal skin biopsies from day 3 compared to baseline and to AK lesion biopsies
• Haemorrhage [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Degree of haemorrhage assessed by histology(binary outcome present/absent) in the Normal skin and AK lesion biopsies at all time points
• Immune cell activation [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Characterisation of immune cells such as T and B lymphocytes, polymorphonuclear cells, mast cells and antigen presenting cells in the Normal skin and AK lesion biopsies
• Apoptosis [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Degree of apoptosis in the Normal skin and AK lesion biopsies
• Endothelium activation [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Degree of vascular endothelium activation in the Normal skin and AK lesion biopsies
• RNA expression [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Changes in mRNA and miRNA expression in the Normal skin and AK lesion biopsies
• Drug Transporter [ Time Frame: From baseline until day 3 ] [ Designated as safety issue: No ]
  Expression of drug transporters in the Normal skin and AK lesion biopsies (P-gP)

This trial will be conducted to explore the biological effects in the skin following treatment with PEP005 Gel, 0.05% administered for two consecutive days, assessed by histology.

Inclusion Criteria:

1. Male or female patients at least 18 years of age
2. Patients with AK lesions within a contiguous 25 cm2 area on the upper extremity
3. Patients with a 25 cm2 area of normal skin on the upper inner arm
4. Female subjects must be of either non-childbearing potential or childbearing potential, provided there is a confirmed negative urine pregnancy test prior to exposure, to rule out pregnancy
5. Female subjects of childbearing potential must be willing to consent to using high effective methods of contraception
6. Ability to follow study instructions and likely to complete all study requirements
7. Obtained written informed consent prior to any study-related procedures

Exclusion Criteria:

1. Location of the selected treatment areas within 5 cm of an incompletely healed wound within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)
2. History or evidence of skin conditions other than the study indication that would interfere with evaluation of the study medication
3. 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, as determined by Investigator clinical judgment.
4. Anticipated need for in-patient hospitalisation or in-patient surgery during the study period.
5. Current participation in any other interventional clinical trial
6. Subjects who have received treatment with any non-marketed drug product within the last two months
7. Subject known or, in the opinion of the investigator, is unlikely to comply with the Clinical Study Protocol
8. Females who are pregnant, of child-bearing potential and wishing to become pregnant during the trial, or are breast feeding
9. Undergone cosmetic or therapeutic procedures within 2 cm of the selected treatment areas in the 2 weeks prior to the screening visit
10. Use of acid-containing therapeutic products within 2 cm of the selected treatment areas in the 2 weeks prior to the screening visit
11. Use of topical salves/topical steroids: within 2 cm of the selected treatment areas in the 2 weeks prior to the screening visit
12. Treatment with immunomodulators, cytotoxic drugs or interferon/interferon inducers, systemic medications that suppress the immune system or UVB in the last 4 weeks
13. Treatment with 5-FU, imiquimod, diclofenac, or photodynamic therapy: within 2 cm of the selected treatment areas within 8 weeks prior to any screening visit
14. Use of systemic retinoids