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

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)

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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: Vehicle; Drug: 5-fluorouracil/salicylic acid

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Almirall Investigational Site #3
  • Berlin, Germany, 13055
    • Almirall Investigational Site #5
  • Berlin, Germany, 13507
    • Almirall Investigational Site #4
  • Bochum, Germany, 44791
    • Almirall Investigational Site #1
  • Bochum, Germany, 44803
    • Almirall Investigational Site #8
  • Bonn, Germany, 53111
    • Almirall Investigational Site #6
  • Dülmen, Germany, 48249
    • Almirall Investigational Site #9
  • Friedrichshafen, Germany, 88045
    • Almirall Investigational Site #10
  • Selters, Germany, 56242
    • Almirall Investigational Site #2
  • Wuppertal, Germany, 42275
    • Almirall Investigational Site #7
• United Kingdom
  • Leicester, United Kingdom, LE10 2SE
    • Almirall Investigational Site #11
  • Nantwich, United Kingdom, CW5 5NX
    • Almirall Investigational Site #12
  • Penzance, United Kingdom, TR18 4JH
    • Almirall Investigational Site #13
  • Penzance, United Kingdom, TR19 7HX
    • Almirall Investigational Site #14

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5-fluorouracil/salicylic acid; 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; Other Names: Actikerall
Placebo Comparator: Vehicle; Vehicle solution applied to the affected area once-daily for 12 weeks	Drug: Vehicle

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Almirall, S.A.
• Collaborators: Almirall Hermal GmbH
• Investigators: Study Director: Wolf-Godehard Ocker, Almirall Hermal GmbH

Publications and helpful links

General Publications

• 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. Erratum In: Dermatol Ther (Heidelb). 2017 Jun;7(2):263.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: November 10, 2014
• First Submitted That Met QC Criteria: November 10, 2014
• First Posted (Estimate): November 13, 2014

Study Record Updates

• Last Update Posted (Estimate): August 5, 2016
• Last Update Submitted That Met QC Criteria: August 3, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Keratolytic Agents; Fluorouracil; Salicylic Acid; Salicylates
• Other Study ID Numbers: 98605101-1401; 2014-001171-31 (EudraCT Number); ALM014 (Other Identifier: Almirall Hermal GmbH)