Actinic Keratosis
Conditions
Brief summary
The main purpose of this vehicle-controlled study is to determine the efficacy and safety of a solution of Actikerall® (containing 5-fluorouracil 0.5% and salicylic acid 10.0%) in the field-directed treatment of grade I-II actinic keratosis, when it is applied to the affected area once daily for 12 weeks. A secondary objective of this study is to evaluate the efficacy of Actikerall® solution on subclinical actinic keratosis lesions in a subset of patients.
Interventions
DRUG5-fluorouracil/salicylic acid
DRUGVehicle
Sponsors
Almirall Hermal GmbH
Almirall, S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or non-pregnant, non-lactating (in the last 3 months) female aged between 18 and 85 years (both inclusive). Women of childbearing potential will follow specific study requirements. * Patients with at least 4 but not more than 10 clinically confirmed actinic keratoses lesions grade I or II (according to Olsen EA et al. 1991) within a field of cancerization of 25 cm² in the face/forehead or bald scalp. * Patients with skin type I to IV (according to Fitzpatrick Skin Types) * Patients free of any significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment area that may interfere with area examination or final evaluation. * Patients in good health condition or free of medical conditions that may interfere with the study results as confirmed by a physical examination, medical history and laboratory analysis. * Patients who accept to refrain from sunbathing, intense UV-light exposure and the solarium during the study duration. * Patients willing to stop using moisturizers and topical treatments with anti-aging products, vitamins A, C, and/or E containing ointments and gels and green tea preparations in the treatment area. * Patients able (physical ability or supportive person) to apply the study preparations correctly and to follow the study procedure and restrictions. * Patients with at least 3 subclinical lesions in the 25 cm² test area (field) clearly separated from each other and the actinic keratoses lesions (additional inclusion criteria for the patients participating on the sub-clinical lesions sub-study).
Exclusion criteria
* Subjects that have received treatment for actinic keratoses within the treatment area in the 3 months previous to Visit 1 (screening). * Subjects that have received prohibited pharmacological or non-pharmacological treatments for any indication other than actinic keratoses within the treatment area before randomization (Visit 2). * Subjects that have received prohibited systemic treatments for any indication before randomization (Visit 2). * Subjects taking phenytoin, methotrexate or sulfonylurea. * Subjects with dermatological diseases in the treatment area or surrounding area that may be exacerbated by the study treatment or may interfere the study assessments (e.g. psoriasis, eczema). * Subjects that have currently malignant or benign tumors of the skin within the treatment area (e.g., malignant melanoma, basal cell carcinoma, squamous cell carcinoma). * Subjects that suffer from any kind of photodermatoses. * Subjects that have evidence of clinically significant unstable medical conditions. * Subjects with known hypersensitivity to any of the trial drugs (5-fluorouracil, salicylic acid), to ingredients of the trial formulation, or to drugs of similar chemical classes * Subjects with allergy against dimethylsulfoxide, ethanol, ethyl acetate, pyroxyline, poly(butyl)methacrylate, and/or methylmethacrylate. * Subjects with dihydropyrimidine dehydrogenase deficiency (DPD deficiency). * Subjects that are currently participating or have participated within the 8 weeks prior to Visit 1 in another clinical trial. * Patients with known drug or alcohol abuse as assessed by the investigator within the 2 years prior to Visit 1. * Subject is institutionalized because of legal or regulatory order.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with complete clinical clearance of actinic keratosis lesions in the treatment field | Week 20 | Complete Clinical Clearance is defined as no clinically visible actinic keratosis lesions in the selected treatment area |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in the total number of actinic keratosis lesions | Week 20 | — |
| Global assessment of efficacy by the physician (Physician Global Assessment) | Week 20 | — |
| Change from baseline in total score of the Dermatology Life Quality Index (DLQI) | Week 20 | — |
| Total score of the patients´ treatment satisfaction questionnaire for medication (TSQM) | Week 20 | — |
| Percentage of patients with partial clinical clearance of actinic keratosis lesions in the treatment field | Week 20 | Partial clearance is defined as a 75% or greater reduction in the number of clinically visible actinic keratosis lesions in the selected treatment area |
| Percentage change from baseline in the three selected actinic keratosis subclinical lesions | Week 20 | Sub-clinical lesions will be determined using reflectance confocal microscopy in a subset of 30 patients |
| Percentage of patients for which the clearance of one pre-defined representative clinical actinic keratosis lesion is confirmed by reflectance confocal microscopy | Week 20 | Determined using reflectance confocal microscopy in a subset of 30 patients |
| The number of patients with adverse events | Week 20 | — |
| Percentage of patients with complete clearance of three pre-defined subclinical actinic keratosis lesions | Week 20 | Sub-clinical lesions will be determined using reflectance confocal microscopy in a subset of 30 patients |
Countries
Germany, United Kingdom
Outcome results
None listed