Long-term Effects of Imiquimod and Diclofenac in Actinic Keratoses (LEIDA 2)

Sponsor

MEDA Pharma GmbH & Co. KG (Industry)

Overall Status

Completed

CT.gov ID

NCT01453179

Collaborator

Siro Clinpharm Germany GmbH (until June 2013) (Other), Accovion GmbH (Industry)

221

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial serves the purpose to compare the long-term effects of a treatment of actinic keratosis - your skin disorder - using Aldara® 5% cream (Imiquimod) or Solaraze® 3% gel (Diclofenac) on the face or the scalp. In particular, it should be found out whether the healing effect of these two medications on the skin lesions (i.e. the damaged skin parts) can be maintained for a prolonged period.

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratosis	Drug: Imiquimod Drug: Diclofenac	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

221 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Long-term Effects of Aldara® 5% Cream and Solaraze® 3% Gel in the Treatment of Actinic Keratoses on the Face or Scalp With Respect to the Risk of Progression to In-situ and Invasive Squamous Cell Carcinoma

Study Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aldara 5% Cream	Drug: Imiquimod One course of treatment (COT) consisting of an overnight application of IMIQ (1 sachet for up to 50 cm2), applied 3 nights per week (e.g. Monday, Wednesday, Friday) for 4 weeks followed by a 4 weeks treatment pause. If necessary, this may be followed by a second COT.
Active Comparator: Solaraze 3% Gel	Drug: Diclofenac Solaraze® is applied locally to the skin 2 times daily and smoothed into the skin gently. The amount needed depends on the size of the lesion. Normally 0.5 grams (the size of a pea) of the gel is used on a 25 cm2 lesion site. The duration of therapy is 12 weeks.

Arm

Intervention/Treatment

Experimental: Aldara 5% Cream

Drug: Imiquimod

One course of treatment (COT) consisting of an overnight application of IMIQ (1 sachet for up to 50 cm2), applied 3 nights per week (e.g. Monday, Wednesday, Friday) for 4 weeks followed by a 4 weeks treatment pause. If necessary, this may be followed by a second COT.

Active Comparator: Solaraze 3% Gel

Drug: Diclofenac

Solaraze® is applied locally to the skin 2 times daily and smoothed into the skin gently. The amount needed depends on the size of the lesion. Normally 0.5 grams (the size of a pea) of the gel is used on a 25 cm2 lesion site. The duration of therapy is 12 weeks.

Outcome Measures

Primary Outcome Measures

Long-term outcome with respect to the risk of progression to SCC (in situ and/or invasive) of treatment with Aldara® 5% cream (IMIQ) and Solaraze® 3% gel (DIC) with increased precision (meta-analysis with study 3271). [3 years]

Secondary Outcome Measures

Recurrence rate [3 years]
Time to recurrence [3 years]
Need of rescue treatment [3 year]
Cosmetic outcome [3 years]
Cosmetic outcome assessed by patient and investigator on a verbal rating scale.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

To be eligible, a patient must comply with all of the following criteria:

Immunocompetent patient.
A study treatment area must be identifiable: Minimum of 5 and maximum of 10 typical visible AKs in one contiguous area of up to 50 cm2 on the face or scalp. The eyelids, the inside of the nostrils or ears, or the lip area inside the vermilion border must not be part of this area.
A positive histological finding for AK grade I or II. This will be determined from the most suspicious lesion in the STA and there from the most pathological area biopsied during screening visit. This analysis will be done by the central histopathological laboratory.
Willingness to comply with the obligations of the study.

Exclusion Criteria:

A patient is ineligible and must not enter the study if any of the following criteria is met:

Safety concerns:

History of hypersensitivity to imiquimod, diclofenac, acetyl salicylic acid, other non steroidal anti-inflammatory drugs (NSAID), hyaluronic acid, or relevant excipients.
Pregnancy, breast-feeding or planned pregnancy during the study. Women of child bearing potential not using a highly effective method of birth control defined as those which result in a low failure rate (i.e. <1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal IUDs, tubal ligation or vasectomised partner.

Lack of suitability for the study:

Presence of AK lesions in the STA with clinically excessive hyperkeratosis as seen in cutaneous horns.
Any topical AK treatment including imiquimod or diclofenac, or any systemic AK treatment such as systemic retinoids, or any surgical AK treatment at the STA within the last 2 months prior to randomisation.
Persisting AK lesion at screening visit following topical treatment with imiquimod or diclofenac in the STA.
Presence of any histologically confirmed skin tumour in the STA: in situ SCC including Bowen's disease, invasive SCC, basal cell carcinoma, or other malignant tumours.
Any dermatological disease or condition that may exacerbate by treatment with imiquimod or diclofenac (e.g. rosacea, psoriasis, atopic dermatitis).
Any dermatological disease or condition in the STA that causes difficulty with examination (e.g. eczema).
Systemic immunomodulatory treatment such as interferon, azathioprine, cyclosporine, retinoids, any oral or injectable corticosteroids, or inhaled or nasal corticosteroids with dosages of >1200 µg/day beclomethasone or equivalent within 4 weeks before start of study treatment.
History of any malignant tumour with high tumour burden or any systemic antitumour treatment (incl. radiotherapy).
History of any malignant skin tumour having metastasised or in which metastasis within the study period is likely.
History of severe cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental, neurological, or other disease within the last two years which might hinder regular treatment and supervision and might lead to premature withdrawal from the study.
Mentally incapacitated patient.
Present or history of drug or alcohol abuse within the last 3 years.

Administrative reasons:

Exposure to an investigational product within the last 3 months.
Lack of ability or willingness to give informed consent.
Age below 18 years.
Lack of willingness to have personal study related data collected, archived or transmitted according to protocol.
Anticipated non-availability for study visits/procedures.
Vulnerable subjects (such as persons kept in detention).

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medical University Graz, University Clinic for Dermatology and Venerology Graz	Graz	Austria	A-8036
2	Medical Practice	Maria Enzersdorf	Austria	A-2344
3	Medical University Vienna, Department for General Dermatology	Vienna	Austria	A-1090
4	Medical Supply Center	Augsburg	Germany	D-86163
5	Licca Clinical Research Institute, Clinic for Dermatolgy and Surgery	Augsburg	Germany	D-86179
6	Medical Practice	Berlin	Germany	D-10437
7	Medical Practice	Duelmen	Germany	D-48249
8	Medical Practice	Germering	Germany	D-82110
9	Medical Department of Otto-von-Guericke-University Magdeburg, University Clinic for Dermatology and Venerology	Magdeburg	Germany	D-39120
10	Medical Practice	Mahlow	Germany	D-15831
11	Department of Dermatology Johannes Gutenberg-University Mainz, Clinical Research Center	Mainz	Germany	D-55131
12	Medical Practice	Markkleeberg	Germany	D-04416
13	Medical Practice for Dermatology and Medical Cosmetics	Mönchengladbach	Germany	D-41061
14	Medical Practice	Münster	Germany	D-48143
15	Derma Center Vechta, Clinic for Dermatology	Vechta	Germany	D-49377
16	Centrovital, Medical Practice for Dermatology	Witten	Germany	D-58453
17	Medical Practice for Dermatology and Venerology	Wuppertal	Germany	D-42275

Sponsors and Collaborators

MEDA Pharma GmbH & Co. KG
Siro Clinpharm Germany GmbH (until June 2013)
Accovion GmbH

Investigators

Study Director: Ursula Petzold, Dr., MEDA Pharma GmbH & Co. KG
Principal Investigator: Harald Gollnick, Prof. Dr., Otto-von-Guericke-University of Magdeburg