Clinical trial NCT02289768: Study To Evaluate The Efficacy And Safety Of Actikerall® Solution In Patients With Grade I-II Actinic Keratoses
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Actinic Keratosis
Lead sponsor: Almirall, S.A.
Sponsor class: INDUSTRY
Collaborators: name: Almirall Hermal GmbH
First posted: 2014-11-13
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of patients with complete clinical clearance of actinic keratosis lesions in the treatment field
timeFrame: Week 20
Secondary outcomes:
measure: Percentage of patients with partial clinical clearance of actinic keratosis lesions in the treatment field
timeFrame: Week 20
measure: Percentage change from baseline in the total number of actinic keratosis lesions
timeFrame: Week 20
measure: Global assessment of efficacy by the physician (Physician Global Assessment)
timeFrame: Week 20
measure: Change from baseline in total score of the Dermatology Life Quality Index (DLQI)
timeFrame: Week 20
measure: Total score of the patients´ treatment satisfaction questionnaire for medication (TSQM)
timeFrame: Week 20
measure: Percentage of patients with complete clearance of three pre-defined subclinical actinic keratosis lesions
timeFrame: Week 20
measure: Percentage change from baseline in the three selected actinic keratosis subclinical lesions
timeFrame: Week 20
measure: Percentage of patients for which the clearance of one pre-defined representative clinical actinic keratosis lesion is confirmed by reflectance confocal microscopy
timeFrame: Week 20
measure: The number of patients with adverse events
timeFrame: Week 20
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Almirall Investigational Site #3
city: Berlin
country: Germany
facility: Almirall Investigational Site #5
city: Berlin
country: Germany
facility: Almirall Investigational Site #4
city: Bochum
country: Germany
facility: Almirall Investigational Site #1
city: Bochum
country: Germany
facility: Almirall Investigational Site #8
city: Bonn
country: Germany
facility: Almirall Investigational Site #6
city: Dülmen
country: Germany
facility: Almirall Investigational Site #9
city: Friedrichshafen
country: Germany
facility: Almirall Investigational Site #10
city: Selters
country: Germany
facility: Almirall Investigational Site #2
city: Wuppertal
country: Germany
facility: Almirall Investigational Site #7
city: Leicester
country: United Kingdom
facility: Almirall Investigational Site #11
city: Nantwich
country: United Kingdom
facility: Almirall Investigational Site #12
city: Penzance
country: United Kingdom
facility: Almirall Investigational Site #13
city: Penzance
country: United Kingdom
facility: Almirall Investigational Site #14
Study officials:
affiliation: Almirall Hermal GmbH
name: Wolf-Godehard Ocker
role: STUDY_DIRECTOR
References:
citation: Stockfleth E, von Kiedrowski R, Dominicus R, Ryan J, Ellery A, Falques M, Ivanoff N, Azeredo RR. Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double-Blind, Vehicle-Controlled Trial. Dermatol Ther (Heidelb). 2017 Mar;7(1):81-96. doi: 10.1007/s13555-016-0161-2. Epub 2016 Dec 19.