Study on the efficacy of Verrumal(R) compared to placebo and Solaraze(R) in the treatment of actinic keratosis grade I to II

• Conditions: Treatment of actinic keratosis grade I to II; MedDRA version: 9.1Level: LLTClassification code 10000614Term: Actinic keratosis

• Registration Number: EUCTR2007-003889-18-DE
• Lead Sponsor: Almirall Hermal GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-10
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot 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 suffering from actinic keratosis grade I or II.
3. Have a general good and stable health condition as confirmed by a physical examination and by medical history.
4. Patients 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 7, 8, 9, 10, 11, 12 and 13 of the exclusion criteria:
- controlled hypertension
- diabetes mellitus type II
- hypercholesterolaemia
- osteoarthritis
5. Skin type I to IV according to Fitzpatrick.
6. Accept to abstain from sunbathing and the solarium during the study.
7. Have at least 4 but not more than 10 clinically confirmed AK target lesions of mild to moderate intensity within the face/forehead or bald scalp (excluding eyelids, lips and mucosa), i. e. actinic keratosis grade I and II according to Olsen EA et al. 1991.
To document the diagnosis of the investigators, the AK-lesions will be photo-documented.
8. The AK lesions must be discrete and quantifiable; the distance from one lesion to its neighbour 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.
Record the size of each baseline AK lesion by measuring the two largest perpendicular diameters. To describe irregular lesions (ellipsoidal) investigators will measure the major and minor axis. Both axes must be above the minimum of 0.5 cm and under the maximum of 1.5 cm.
10. The whole area to be treated (test area) must not be greater than 25 scm. 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 preparations 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. A female is considered to be of childbearing potential if she possesses an uterus and at least one ovary, has not had a tubal ligation, or she is not at least 3 years postmenopausal. Highly effective methods of birth control are defined as resulting in a low failure rate (Pearl Index below 1, failure rate less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. The use of condoms without spermicide coating is not considered to be 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, diclofenac sodium, salicylic acid, acetylsalicylic acid and other non-steroid antirheumatic agents.
3. Are patients under immunosuppression therapy.
4. Have inherited or acquired coagulation defects.
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. 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:
Topical retinoids (6 weeks), Topical steroids (4 weeks), Topical diclofenac reparations (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 chemodestruction (6 weeks), Photodynamic therapy (6 weeks), Therapeutic UV-Radiation (6 weeks).
9. Have received the following systemic treatments within the designated period before treatment with study drug:
Interferon (6 weeks), Immunomodulators or immuno-suppressive therapies (12 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 corticosteroids (>1200 µg/day for beclomethasone,
or >600 µg/day for fluticasone; 4 weeks).
10. Patients taking phenytoin, methotrexate or sulfonylurea.
11. Patients taking inhibitors of DPD (e.g. Brivudin, Sorivudin)
12. Known allergy against dimethylsulfoxide, ethanol, ethyl acetate, pyroxyline, poly(butyl)methacrylate, methylmethacrylate, sodium hyaluronate, benzyl alcohol, poly ethyleneglycol monomethyl ether.
13. Known DPD deficiency.
14. Are known to be pregnant or lactating (currently or within the past 3 months).
15. Have any dermatological disease in the treatment area or surrounding area that may be exacerbated by treatment with topical Verrumal® or Solaraze® gel or cause difficulty with examination (e.g. psoriasis, eczema, dermatitis exfoliativa).
16. Show Cornu cutaneum like alterations of the skin in the face or on the bald scalp (target area).
17. Are currently or within the past 8 weeks participating in another clinical study.
18. Have active chemical dependency or alcoholism as assessed by the investigator.
19. Patient is institutionalized because of legal or regulatory order.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Superiority to placebo and non-inferiority to Solaraze with respect to histological clearance of target lesion.;Secondary Objective: - Superiority to Solaraze with respect to histological clearance of target lesion.<br>- Improvement of treated lesions (lesion response).<br>- Tolerability and safety by physicans global assessment score (PGA, PGT).<br>- Tolerability and efficacy by patient's assessment and patient's compliance;Primary end point(s): histological status of target lesion (cleared, not cleared) 8 weeks post treatment end<br>