biological effects of leo 43204 in actinic keratosis

Conditions: Actinic Keratosis

Summary: this is a phase i, single-centre, open label, within-subject comparison trial to explore the biological effects of leo 43204 gel, 0.037%, applied once daily for 3 consecutive days in patients with actinic keratosis on the upper extremity. the treatment area for each patient will be as defined as a contiguous area of 250 cm2 of skin on the upper extremity (including the dorsum manus) that contains a minimum of 5 ak lesions. additionally there must be at least one ak lesion located in a non-treated area on the contralateral arm. all eligible subjects will receive leo 43204 gel, 0.037%, on the treatment area on days 1, 2 and 3. study medication application will be (sub)investigator applied. a total of 30 patients will be enrolled into this study (n=15 in each of the two groups). patients will be divided into two groups with different biopsy schedules.


Eligibility criteria:
inclusion criteria: * 1. signed and dated informed consent has been obtained. * 2. subjects with at least 5 non-keratotic, clinically typical, visible and discrete ak lesions within a contiguous 250 cm2 area (ak treatment area) on the upper extremity, * 3. subjects with one additional ak lesion located on the contralateral arm. * 4. subjects with an area of normal skin in close proximity to the ak treatment area or on the contralateral arm. * 5. male and female subjects, 18 years or older. * 6. agreement from the patient to allow photographs of the selected treatment area to be taken and used as part of the study data package * 7. ability to follow study instructions and likely to complete all study requirements * 8. 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 has tubal litigation) or, * child-bearing potential\* provided there is a confirmed negative pregnancy test prior to trial treatment to rule out pregnancy. * female subjects are considered of child-bearing potential unless they have had a hysterectomy or have undergone tubal litigation or have been post-menopausal for at least one year prior to first visit. * 9. female subjects of child-bearing potential must be willing to use effective contraception at trial entry and until completion. effective contraception is defined as follows: * abstinence (when this is in line with the preferred and usual life style of the subject). * vasectomised partner (given that the subject is monogamous). * an intrauterine device. * double barrier method defined as two distinct methods (two actual barrier methods). * hormonal contraceptive (oral hormonal birth control, oestrogenic vaginal ring, percutaneous contraceptive patches, implants and injectables) for at least one menstrual cycle prior to enrolment. exclusion criteria: * 1. prior treatment with ingenol mebutate gel in the treatment area within the last 12 months. * 2. previously assigned treatment in this clinical trial or previously participated in a clinical trial in the leo 43204 programme (presently lp0084-68, lp0084-1013, lp0084-1014, lp0084-1015, lp0084-1148, lp0084-1077, lp0084-1193, lp0084-1194, lp0084-1195, lp0084-1196). * 3. location of the selected treatment area within 5 cm of an incompletely healed wound or infected area of the skin (excl. study related biopsies) or within 5 cm of a suspected basal cell carcinoma (bcc) or scc. * 4. history or evidence of skin conditions other than the study indication that would interfere with the histologically- or biomarker evaluation of the study medication (e.g. eczema, unstable psoriasis, xeroderma pigmentosum). * 5. treatment area lesions that have an atypical clinical appearance (e.g. hypertrophic, hyperkeratotic, recalcitrant disease \[had cryosurgery on two previous occasions\] and/or cutaneous horns). * 6. known sensitivity or allergy to any of the ingredients of leo 43204 gel (e.g. citric acid) * 7. 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 during the course of the study, as determined by investigator clinical judgment. * 8. anticipated need for in-patient hospitalisation or in-patient surgery during the study period. note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in the prohibited therapies or medications (listed below). * 9. anticipated excessive or prolonged exposure to ultraviolet light (e.g. sunlight) or use of tanning beds for the duration of the study * 10. current participation in any other interventional clinical trial * 11. subjects who have received treatment with any non-marketed drug product (i.e. an agent which has not yet been made available for clinical use following registration) within the last two months. * 12. subjects known to be infected with human immunodeficiency virus (hiv). * 13. subject known or, in the opinion of the investigator, is unlikely to comply with the clinical study protocol (e.g. alcoholism, drug dependency or psychotic state). * 14. females who are pregnant, of child-bearing potential and wishing to become pregnant during the trial, or are breast feeding. * 15. females of child-bearing potential with positive pregnancy test at \[screening or visit 1\]. * 16. previous enrolment in this clinical trial. prohibited therapies and/or medications: within 2 weeks prior to the screening visit * 17. cosmetic or therapeutic procedures (e.g. use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing): within 2 cm of the selected treatment areas and within 2 cm of the selected ak lesion outside the treatment area * 18. use of acid-containing therapeutic products (e.g. salicylic acid or fruit acids, such as alpha and beta hydroxy acids and glycolic acids), topical retinoids or light chemical peels: within 2 cm of the selected treatment areas and within 2 cm of the selected ak lesion outside the treatment area * 19. use of topical salves (non-medicated/non-irritant lotion/cream are acceptable) or topical steroids: within 2 cm of the selected treatment areas and within 2 cm of the selected ak lesion outside the treatment area; artificial tanners: within 5 cm of the selected treatment areas and within 5 cm of the selected ak lesion outside the treatment area prohibited therapies and/or medications: within 4 weeks prior to the screening visit * 20. treatment with immunomodulators (e.g. azathioprine), cytotoxic drugs (e.g. cyclophosphamide, vinblastine, chlorambucil, methotrexate, podophyllin, camptothecin) or interferon/interferon inducers. * 21. treatment with systemic medications that suppress the immune system (e.g. cyclosporine, prednisone, methotrexate, infliximab). * 22. treatment/therapy with uvb prohibited therapies and/or medications: within 8 weeks prior to the screening visit * 23. treatment with 5-fu, imiquimod, diclofenac, or photodynamic therapy: within 2 cm of the selected treatment areas and within 2 cm of the selected ak lesion outside the treatment area prohibited therapies and/or medications: within 6 months prior to the screening visit * 24. use of systemic retinoids (e.g. isotretinoin, acitretin, bexarotene)