A Study of Increasing Strengths, Safety and Efficacy of Two Formulas of LEO 43204 on the Face or the Chest in Patients With Actinic Keratosis

Part 1:

To identify Maximum Tolerated Dose (MTD) levels of two formulations of LEO 43204 after once daily treatment for two consecutive days

Part 2:

To evaluate efficacy of two formulations of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle formulations


Eligibility Criteria:
Inclusion Criteria:

1. Following verbal and written information about the trial, subject must provide informed consent documented by signing the Informed Consent Form (ICF) prior to any trial-related procedures.
2. Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face
3. Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face or within a contiguous area of approximately 250 cm2 (40 in2) on the chest
4. Subject at least 18 years of age.
5. Female subjects must be of either:

   1. Non-childbearing potential, i.e., have a confirmed clinical history of sterility (e.g., the subject is without a uterus or have tubal ligation), or,
   2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment.
6. Female subjects of childbearing potential must use effective contraception throughout the study.

Exclusion Criteria:

1. Location of the treatment area within 5 cm (2 inches) of:

   1. an incompletely healed wound,
   2. a suspected basal or squamous cell carcinoma.
2. Prior treatment with ingenol mebutate gel on the treatment area.
3. Lesions in the treatment areas that have:

   1. atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or
   2. recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions).
4. 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, Rosacea), at the investigator's discretion.
5. Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
6. Any other disease or medical condition such as history or presence of cancer, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunological, or neurological disease or disorder, that, in the opinion of the investigator, makes the subject unsuitable to participate in the trial.
7. Any abnormal laboratory or ECG findings that are clinically significant and would impact the safety of the subjects or the interpretation of the study results, as determined by the investigator.
8. 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.
9. Known sensitivity or allergy to any of the ingredients in the LEO 43204.
10. Presence of acute sunburn within the treatment areas.
11. Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.
12. Subjects previously randomised in the trial (Part 1 or 2).
13. Female subjects who are breastfeeding.
14. 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).