Long-term Effects of Imiquimod and Diclofenac in Actinic Keratoses (LEIDA 2)

Inclusion criteria

To be eligible, a patient must comply with all of the following criteria:

• Immunocompetent patient.
• A study treatment area must be identifiable: Minimum of 5 and maximum of 10 typical visible AKs in one contiguous area of up to 50 cm2 on the face or scalp. The eyelids, the inside of the nostrils or ears, or the lip area inside the vermilion border must not be part of this area.
• A positive histological finding for AK grade I or II. This will be determined from the most suspicious lesion in the STA and there from the most pathological area biopsied during screening visit. This analysis will be done by the central histopathological laboratory.
• Willingness to comply with the obligations of the study.

Exclusion criteria

A patient is ineligible and must not enter the study if any of the following criteria is met:

Safety concerns:

• History of hypersensitivity to imiquimod, diclofenac, acetyl salicylic acid, other non steroidal anti-inflammatory drugs (NSAID), hyaluronic acid, or relevant excipients.
• Pregnancy, breast-feeding or planned pregnancy during the study. Women of child bearing potential not using a highly effective method of birth control defined as those which result in a low failure rate (i.e. <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, tubal ligation or vasectomised partner.

Lack of suitability for the study:

• Presence of AK lesions in the STA with clinically excessive hyperkeratosis as seen in cutaneous horns.
• Any topical AK treatment including imiquimod or diclofenac, or any systemic AK treatment such as systemic retinoids, or any surgical AK treatment at the STA within the last 2 months prior to randomisation.
• Persisting AK lesion at screening visit following topical treatment with imiquimod or diclofenac in the STA.
• Presence of any histologically confirmed skin tumour in the STA: in situ SCC including Bowen's disease, invasive SCC, basal cell carcinoma, or other malignant tumours.
• Any dermatological disease or condition that may exacerbate by treatment with imiquimod or diclofenac (e.g. rosacea, psoriasis, atopic dermatitis).
• Any dermatological disease or condition in the STA that causes difficulty with examination (e.g. eczema).
• Systemic immunomodulatory treatment such as interferon, azathioprine, cyclosporine, retinoids, any oral or injectable corticosteroids, or inhaled or nasal corticosteroids with dosages of >1200 µg/day beclomethasone or equivalent within 4 weeks before start of study treatment.
• History of any malignant tumour with high tumour burden or any systemic antitumour treatment (incl. radiotherapy).
• History of any malignant skin tumour having metastasised or in which metastasis within the study period is likely.
• History of severe cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental, neurological, or other disease within the last two years which might hinder regular treatment and supervision and might lead to premature withdrawal from the study.
• Mentally incapacitated patient.
• Present or history of drug or alcohol abuse within the last 3 years.

Administrative reasons:

• Exposure to an investigational product within the last 3 months.
• Lack of ability or willingness to give informed consent.
• Age below 18 years.
• Lack of willingness to have personal study related data collected, archived or transmitted according to protocol.
• Anticipated non-availability for study visits/procedures.
• Vulnerable subjects (such as persons kept in detention).