Study To Evaluate The Efficacy And Safety Of Actikerall® Solution In Patients With Grade I-II Actinic Keratoses

Study Overview
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Brief Summary
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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.

Official Title
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Multicentre, Randomized, Parallel, Double-Blind, Vehicle Controlled Study To Evaluate The Efficacy And Safety Of Actikerall® Solution In The Field-Directed Treatment Of Actinic Keratoses Grade I To II (Field Cancerization)

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: 5-fluorouracil/salicylic acid
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-fluorouracil/salicylic acid<br>Actikerall® solution (5-fluorouracil 0.5%, salicylic acid 10.0%) applied to the affected area once-daily for 12 weeks | Drug: 5-fluorouracil/salicylic acid<br> <br> * Other names: Actikerall;|
| Placebo Comparator: Vehicle<br>Vehicle solution applied to the affected area once-daily for 12 weeks | Drug: Vehicle<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with complete clinical clearance of actinic keratosis lesions in the treatment field | Complete Clinical Clearance is defined as no clinically visible actinic keratosis lesions in the selected treatment area | Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with partial clinical clearance of actinic keratosis lesions in the treatment field | Partial clearance is defined as a 75% or greater reduction in the number of clinically visible actinic keratosis lesions in the selected treatment area | Week 20 | 
| 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 complete clearance of three pre-defined subclinical actinic keratosis lesions | Sub-clinical lesions will be determined using reflectance confocal microscopy in a subset of 30 patients | Week 20 | 
| Percentage change from baseline in the three selected actinic keratosis subclinical lesions | Sub-clinical lesions will be determined using reflectance confocal microscopy in a subset of 30 patients | Week 20 | 
| Percentage of patients for which the clearance of one pre-defined representative clinical actinic keratosis lesion is confirmed by reflectance confocal microscopy | Determined using reflectance confocal microscopy in a subset of 30 patients | Week 20 | 
| The number of patients with adverse events |  | Week 20 |