Three-armed, randomized, double-blind dose-finding trial on efficiency and safety of Ibuprofen 5% gel, Ibuprofen 7,5% gel und Ibuprofen 10% gel in patients with actinic keratosis Olsen grade I/II

INTERVENTION: Product Name: Ibuprofen 5% Gel Pharmaceutical Form: Gel INN or Proposed INN: IBUPROFEN CAS Number: 15687‐27‐1 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 50‐ Product Name: Ibuprofen 7,5% Gel Pharmaceutical Form: Gel INN or Proposed INN: IBUPROFEN CAS Number: 15687‐27‐1 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 75‐ Product Name: Ibuprofen 10% Gel Pharmaceutical Form: Gel INN or Proposed INN: IBUPROFEN CAS Number: 15687‐27‐1 Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 100‐ CONDITION: Actinic keratosis Olsen grade I/II ; MedDRA version: 16.1 Level: PT Classification code 10000614 Term: Actinic keratosis System Organ Class: 10040785 ‐ Skin and subcutaneous tissue disorders Therapeutic area: Diseases [C] ‐ Skin and Connective Tissue Diseases [C17] PRIMARY OUTCOME: Main Objective: In this three‐armed dose‐finding trial 3 ibuprofen‐gels (5%, 7.5% and 10% concentration of the active agent) shall be investigated with respect to safety and efficacy in order to identify the optimal ibuprofen concentration in the gel formulation.; The main objective of the trial is to determine the optimal concentration of the active agent in the gel formulation as quantified by the change of the number of keratosis (assessed by the target lesion number score ‐ TLNS) in pre‐defined areas in a time period from inclusion in the trial until the end of treatment (3 months) or prior complete healing.; Primary end point(s): Change of Target Lesion Number Score (mean) during treatment period Secondary Objective: Secondary objectives are the change of visible keratosis during the treatment period as assessed by the investigator global improvement index (IGII) and the patient global improvement index (PGII) using a scale ranging from ‐2 (serious worsening) to +4 (healed) as well as the local skin/ dermal tolerance of the IMP and, if so, adverse events. Timepoint(s) of evaluation of this end point: During treatment period (90 days) SECONDARY OUTCOME: Secondary end point(s): ‐ Change of visible keratosis during treatment period as assessed by the Investigator Global Improvement Index (IGII) and the Patient Global Improvement Index (PGII); ‐ Tolerance of the investigated medicinal product; ‐ Adverse events; Timepoint(s) of evaluation of this end point: During treatment period (90 days) INCLUSION CRITERIA: ‐ Age: = 18 years ‐ Gender: male and female ‐ Actinic Keratosis (Olsen grade I/II) ‐ at least 5 aktinic keratoses on the scalp, forehead, face, extremities, and/ or decolleté ‐ no treatment of the actinic keratoses within the previous 3 months before inclusion in the study ‐ histologic confirmation of the diagnosis actinic keratosis by biopsy ‐ good general condition ‐ normal laboratory values (creatinine, urea, GOT, GPT, GGT, LDH) and blood count at study start not higher than 1.5 x upper norm limit ‐ Female patients must be tested negative for pregnancy before inclusion in the trial. During the trial, female patients have to apply a generally accepted form of birth control (i.e. oral estrogen‐ and gestagen‐containing contraceptives; estrogen containing skin plaster/ tape, hormone implant, hormone contraceptive coil, sterilisation; sexual abstinence) or being post‐menopausal for at least 2 years. ‐ Willing and able to participate in t