Patients aged 18 and older suffering from actinic keratosis. Patients to be considered have at least 6 but no more than 16 clinically confirmed AK target lesions of mild to moderate intensity in up to 3 treatment areas (TAs) with a size of 25 cm2 per TA (i.e. total size of TA is up to 75 cm2) and additionally one representative AK lesion for histological diagnosis of AK, which must be located in the face including the forehead (excluding eyelids, lips and mucosa) and/or bald scalp. MedDRA versi
Conditions
Interventions
Product Name: LAS41007 (5% diclofenac gel)
Product Code: LAS41007 (5% diclofenac gel)
Pharmaceutical Form: Gel
INN or Proposed INN: DICLOFENAC SODIUM
CAS Number: 15307-79-6
Other descriptive name: DIC
Sponsors
Almirall S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent, 2. Caucasian male and female patients, 3. Aged = 18 years, 4. Women of childbearing potential are allowed to participate in this study, only if they use a highly effective method of contraception , 5. Have at least 6 but no more than 16 clinically confirmed AK target lesions of mild to moderate (grade I to II, according to Olsen et al, 1991) intensity in the whole treatment area (TA) (and additionally one representative AK lesion for histological diagnosis of AK), which must be located in the face including the forehead (excluding eyelids, lips and mucosa) and/or bald scalp, 6. The AK target lesions must be discrete and quantifiable; the distance from one lesion to its neighbor lesion must be greater than 1.0 cm, 7. The diameter of each AK target lesion should be not less than 0.5 cm and not greater than 1.5 cm, 8. The target lesions must be located in up to 3 TAs with a size of 25 cm2 per TA (i.e. total area of TA is up to 75 cm2), 9. Patient consents to take punch biopsies in the TA. Additionally, to be eligible for randomization, a patient must comply with the following criterion: 10. Diagnosis of AK histologically confirmed by result of punch biopsy taken at screening visit (classification according to Röwert-Huber, 2007). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 107 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 717
Exclusion criteria
Exclusion criteria: 1. Have known hypersensitivity, intolerance or allergies against diclofenac sodium or other ingredients of the IMPs (hyaluronic acid, benzyl alcohol, poly ethyleneglycol monomethyl ether) and other non-steroidal anti-inflammatory agents, 2. Have a history of bronchospasm, asthma, urticaria, or rhinitis after the intake of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs), 3. Have a history of gastrointestinal bleeding or perforation associated with prior therapy with NSAIDs, 4. Have evidence of clinically significant or unstable medical conditions such as: - metastatic tumor or tumor with high probability of metastatic spread, - heart failure (NYHA class III or higher), - immunosuppressive disorder (e.g. HIV, patients following organ transplantation) - hematologic, hepatic, renal, neurologic or endocrine disorder, - collagen-vascular disorder (e.g. cerebro-vascular disorder or other bleedings), - gastrointestinal disorder (e.g. active ulcera or history of recurrent peptic ulcera or hemorrhage), 5. Have currently and within the past 3 months other malignant tumors of the skin in the treatment areas (e.g. malignant melanoma, basal cell carcinoma, squamous cell carcinoma), 8. Are known to be pregnant or lactating (currently or within the past 3 months), 10. Have received the following topical treatments for any indication in the target area (defined as the whole face, including the forehead and the bald scalp) within 6 weeks before treatment with IMP: topical retinoids, topical steroids, topical 5-fluorouracil preparations, topical immunomodulators, topical diclofenac, 11. Have received the following physical treatments in the TAs within the designated period before treatment with IMP: treatment (6 weeks), surgical excision - except biopsy for diagnostic confirmation (6 weeks), cryo-, thermo- or chemodestruction (6 weeks), photodynamic therapy (6 weeks), curettage (4 weeks), 16. Anticoagulative therapy, e.g. with cumarines (e.g. phenprocoumon - e.g. trade name Marcumar® - or heparines throughout the interventional phase of the study. Treatment with ASA at a dose not exceeding 100 mg/d and clopidogrel at a dose not exceeding 75 mg/d will be allowed, 17. Patients having any significant physical abnormalities (e.g. tattoos, dermatoses) in the potential treatment areas that may cause difficulty with examination or final evaluation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are to show: • superiority of LAS41007 compared to vehicle • superiority of LAS41007 compared to Solaraze® in the treatment of clinically confirmed grade I and II AK, each assessed by histology to evaluate the histological clearance of one pre-selected target lesion at 60 days post-treatment (PT, V6). ;Secondary Objective: The secondary objectives are to show: • superiority of LAS41007 compared to vehicle • improved clinical efficacy of LAS41007 compared to Solaraze® in the treatment of clinically confirmed grade I and II AK with respect to clinical efficacy. Clinical efficacy will be assessed by: • AK lesion count (TLNS) to evaluate the complete clinical clearance (TLNS = 0) of all target lesions in the treatment area at 60 days PT (V6). • Additional clinical efficacy parameters, e.g. rate of clinical clearance and rate of responders, reduction of total AK target lesion area per patient, improvement of target lesions. Safety will be determined by incidence of adverse events, tolerability (overall and local), laboratory variables, vital signs and the patient's compliance. The objective of the non-interventional phase is to determine the maintenance of sustained complete clinical clearance, recurrences, and the incidence of squamous cell carcinoma.;Primary end point(s): The histological clearance of the (second) pre-selected target lesion at 60 days PT (V6).;Timepoint(s) of evaluation of this end point: 60 days post treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. complete clinical clearance (target lesions); 2. responder rate (target lesions); 3. responder rate (cumulative lesions); 4. rate of clearance; 5. reduction of target lesion area per patient; 6. reduction of overall target lesion area; 6. AK severity scoring; 7. Inv. Global Improv. Index; 8. Patient Global Improv. Index; 9. Dermatol. Qual. of Life Quest.;Timepoint(s) of evaluation of this end point: nos. 1-3, 6: 60 days post treatment; nos. 4-6: from baseline to each study visit; no. 7: at each visit after baseline; no. 8: at End of Treatment visit & 60 days post treatment; 9. at baseline & 60 days post treatment | — |
Countries
Germany, United Kingdom
Contacts
Public ContactClinical Project Leader
Almirall Hermal GmbH
Outcome results
None listed