A prospective comparator controlled randomized exploratory study on the efficacy of LAS 41005 compared to cryotherapy in subjects with hyperkeratotic actinic keratosis

Active, not recruiting

• Conditions: Actinic keratosis; MedDRA version: 12.1Level: LLTClassification code 10000614Term: Actinic keratosis

• Registration Number: EUCTR2010-022980-37-DE
• Lead Sponsor: Almirall Hermal GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-19
• Last Update Posted: 3 June 2013

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Signed and dated written informed consent.
2. Men and women aged between 18 and 85 years inclusive.
3. Have a general good and stable health condition as confirmed by a physical examination and by medical history.
4. Subjects with clinically stable medical conditions including, but not limited to the following diseases will be allowed to be included into the study, if the medication taken for the treatment of the disease does not match the criteria of the excluded or disallowed medications listed in points 8, 9, 10, 11 and 12 of the exclusion criteria:
• controlled hypertension
• diabetes mellitus type II
• hypercholesterolaemia
• osteoarthritis
5. Skin type I to IV according to Fitzpatrick’s
6. Accept to abstain from sunbathing and the solarium during the study.
7. Have at least 4 but not more than 10 clinically confirmed hyperkeratotic AK target lesions of moderate to severe intensity within the face/forehead or bald scalp (excluding eyelids, lips, mucosa and concha), i. e. actinic keratosis grade II and III according to Olsen et al., 1991.
8. The AK lesions must be discrete and quantifiable; the distance from one lesion to its neighbor lesion is greater than 1.0 cm
9. The diameter of each AK lesion is not less than 0.5 cm and not greater than 1.5 cm.
10. The area to be treated (i.e. the AK area plus 5 mm surrounding area) must not be greater 25 cm2. Quantity of lesions to be treated must be adapted accordingly.
11. Are free of any significant physical abnormalities (e.g., tattoos, dermatoses) in the potential treatment area that may cause difficulty with examination or final evaluation.
12. Are willing to stop using moisturizers and any other topical treatments with anti-aging products, vitamin A, vitamin C, and/or vitamin E containing ointments and gels, and green tea preparations during the study within the treatment area. Sunscreens not containing vitamin E will be allowed, but should not be applied in the treatment area within approximately 24 hours before a clinical visit with lesion count.
13. Physical ability to apply the study preparation correctly and to follow the study restrictions and visit.
14. Women of childbearing potential are allowed to participate in this study, only if they use a highly effective method of contraception

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Have received treatment of AK within the treatment area (face / scalp) in the three months preceding this clinical trial.
2. Have known hypersensitivity to 5-fluorouracil or salicylic acid, acetylsalicylic acid .
3. Are subjects under immunosuppressive therapy.
4. Having coagulation defects which are inherited or acquired due to the intake of e.g. coumarine derivates (as Marcumar or Falithrom).
5. Have evidence of clinically significant, unstable medical conditions such as:
• metastatic tumor or tumor with high probability of metastatic spread
• cardiovascular (NYHA class III, IV)
• immunosuppressive
• hematologic, hepatic, renal, neurologic, endocrine
• collagen-vascular
• gastrointestinal
6. Have currently other malignant or benign tumors of the skin within the treatment area (e.g., malignant melanoma, basal cell carcinoma, squamous cell carcinoma).
7. Suffer from paresthesia
8. Suffer from Morbus Raynaud or sclerodermia or CREST-syndrom
9. Have received the following treatments for any indication except for AK in the treatment area within the designated time period before treatment with study drug (treatment, time period):
Topical retinoids, 6 weeks; topical steroids, 4 weeks; topical diclofenac preparations, 6 weeks; topical 5-fluorouracil preparations, 6 weeks; topical immunomodulators, 6 weeks; surgical excision (except biopsy for diagnostic confirmation), 6 weeks; curettage, 4 weeks; cryo-, thermo- or chemo-destruction, 6 weeks; photodynamic therapy, 6 weeks; therapeutic UV-radiation, 6 weeks
10. Have received the following systemic treatments within the designated period before treatment with study drug (treatment, time period):
Interferon, 6 weeks; immunomodulators or immunosuppressive therapies, 12 weeks;
diclofenac preparations, 6 weeks; 5-fluorouracil preparations, 6 weeks; cytotoxic drugs, 6 months; investigational drugs, 8 weeks; drugs known to have major organ toxicity, 8 weeks; corticosteroids (oral or injectable), 6 weeks; inhaled cortico-steroids (>1200 mcg/day for beclomethasone, or >600 mcg/day for fluticasone), 4 weeks
11. Subjects taking phenytoin, methotrexate or sulfonylurea.
12. Subjects taking inhibitors of DPD (e.g. Brivudin, Sorivudin)
13. Known allergy against dimethylsulfoxide, ethanol, ethyl acetate, pyroxyline, poly(butyl)methacrylate, methylmethacrylate.
14. Known DPD-deficiency.
15. Known cryoglobulinaemia or cold intolerance
16. Are known to be pregnant or lactating (currently or within the past 3 months).
17. Have any dermatological disease in the treatment area or surrounding area that may be exacerbated by treatment with topical LAS 41005 or cryotherapy or cause difficulty with examination (e.g. psoriasis, eczema, dermatitis exfoliativa, cold urticaria, blister-forming dermatosis).
18. Show cornu cutaneum like alterations in the target area.
19. Are currently or within the past 8 weeks participating in another clinical study.
20. Have active chemical dependency or alcoholism as assessed by the investigator.
21. Subject is institutionalized because of legal or regulatory order.
Topical diclofenac (e.g. Voltaren® Emulgel) and steroids for the treatment of dermatological diseases (e.g. atopic dermatitis, lichen planus) in locations other than the treatment area will be allowed during the study provided the amount used, does not exceed 2 mg fluorinated steroids daily for more than 1 week or 6 mg beclomethasone for more than 1 week.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy and safety of LAS 41005 compared to cryotherapy in subjects with moderate to severe hyperkeratotic actinic keratosis (confirmed by punch biopsies).;Secondary Objective: ;Primary end point(s): Histological clearance at 8 weeks after end of treatment with LAS 41005, respectively 14 weeks after first cryotherapy