## Protocol Section
### Identification Module
**NCT ID:** NCT01453179

**Acronym:** LEIDA 2

**Brief Title:** Long-term Effects of Imiquimod and Diclofenac in Actinic Keratoses (LEIDA 2)

**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

#### Organization Study ID Info
**ID:** X-03016-3284
#### Organization
**Class:** INDUSTRY
**Full Name:** Viatris Inc.
#### Secondary ID Infos
**ID:** 2010-022054-16
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2015-03

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-02-07

**Type:** ACTUAL

**Last Update Submit Date:** 2022-02-04

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2015-03

**Type:** ACTUAL

#### Start Date
**Date:** 2011-10

**Status Verified Date:** 2015-04

#### Study First Post Date
**Date:** 2011-10-17
**Type:** ESTIMATED
**Study First Submit Date:** 2011-09-30
**Study First Submit QC Date:** 2011-10-12
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** Siro Clinpharm Germany GmbH (until June 2013)

**Class:** INDUSTRY

**Name:** Accovion GmbH

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** MEDA Pharma GmbH & Co. KG

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Actinic Keratosis

**Keywords:**

- actinic keratosis

- invasive SCC

- in situ SCC

- histological classification

- histological progression

- clinical clearance

- cryotherapy

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 221

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Imiquimod

**Label:** Aldara 5% Cream

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: Diclofenac

**Label:** Solaraze 3% Gel

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Aldara 5% Cream

**Description:** 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.

**Name:** Imiquimod

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Solaraze 3% Gel

**Description:** 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.

**Name:** Diclofenac

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** 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).

**Time Frame:** 3 years

#### Secondary Outcomes

**Measure:** Recurrence rate

**Time Frame:** 3 years

**Measure:** Time to recurrence

**Time Frame:** 3 years

**Measure:** Need of rescue treatment

**Time Frame:** 3 year

**Description:** Cosmetic outcome assessed by patient and investigator on a verbal rating scale.

**Measure:** Cosmetic outcome

**Time Frame:** 3 years

### Eligibility Module

**Eligibility Criteria:** 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).

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Graz

**Country:** Austria

**Facility:** Medical University Graz, University Clinic for Dermatology and Venerology Graz

**Zip:** A-8036

**Location 2:**

**City:** Maria Enzersdorf

**Country:** Austria

**Facility:** Medical Practice

**Zip:** A-2344

**Location 3:**

**City:** Vienna

**Country:** Austria

**Facility:** Medical University Vienna, Department for General Dermatology

**Zip:** A-1090

**Location 4:**

**City:** Augsburg

**Country:** Germany

**Facility:** Medical Supply Center

**Zip:** D-86163

**Location 5:**

**City:** Augsburg

**Country:** Germany

**Facility:** Licca Clinical Research Institute, Clinic for Dermatolgy and Surgery

**Zip:** D-86179

**Location 6:**

**City:** Berlin

**Country:** Germany

**Facility:** Medical Practice

**Zip:** D-10437

**Location 7:**

**City:** Duelmen

**Country:** Germany

**Facility:** Medical Practice

**Zip:** D-48249

**Location 8:**

**City:** Germering

**Country:** Germany

**Facility:** Medical Practice

**Zip:** D-82110

**Location 9:**

**City:** Magdeburg

**Country:** Germany

**Facility:** Medical Department of Otto-von-Guericke-University Magdeburg, University Clinic for Dermatology and Venerology

**Zip:** D-39120

**Location 10:**

**City:** Mahlow

**Country:** Germany

**Facility:** Medical Practice

**Zip:** D-15831

**Location 11:**

**City:** Mainz

**Country:** Germany

**Facility:** Department of Dermatology Johannes Gutenberg-University Mainz, Clinical Research Center

**Zip:** D-55131

**Location 12:**

**City:** Markkleeberg

**Country:** Germany

**Facility:** Medical Practice

**Zip:** D-04416

**Location 13:**

**City:** Mönchengladbach

**Country:** Germany

**Facility:** Medical Practice for Dermatology and Medical Cosmetics

**Zip:** D-41061

**Location 14:**

**City:** Münster

**Country:** Germany

**Facility:** Medical Practice

**Zip:** D-48143

**Location 15:**

**City:** Vechta

**Country:** Germany

**Facility:** Derma Center Vechta, Clinic for Dermatology

**Zip:** D-49377

**Location 16:**

**City:** Witten

**Country:** Germany

**Facility:** Centrovital, Medical Practice for Dermatology

**Zip:** D-58453

**Location 17:**

**City:** Wuppertal

**Country:** Germany

**Facility:** Medical Practice for Dermatology and Venerology

**Zip:** D-42275

#### Overall Officials

**Official 1:**

**Affiliation:** MEDA Pharma GmbH & Co. KG

**Name:** Ursula Petzold, Dr.

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Otto-von-Guericke-University of Magdeburg

**Name:** Harald Gollnick, Prof. Dr.

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Gollnick H, Dirschka T, Ostendorf R, Kerl H, Kunstfeld R. Long-term clinical outcomes of imiquimod 5% cream vs. diclofenac 3% gel for actinic keratosis on the face or scalp: a pooled analysis of two randomized controlled trials. J Eur Acad Dermatol Venereol. 2020 Jan;34(1):82-89. doi: 10.1111/jdv.15868. Epub 2019 Sep 12.

**PMID:** 31407414

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012871

- Term: Skin Diseases

- ID: D000011230

- Term: Precancerous Conditions

- ID: D000009369

- Term: Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M28268

- Name: Keratosis, Actinic

- Relevance: HIGH

- As Found: Actinic Keratosis

- ID: M10668

- Name: Keratosis

- Relevance: HIGH

- As Found: Keratosis

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M5550

- Name: Carcinoma, Squamous Cell

- Relevance: LOW

- As Found: Unknown

- ID: M20559

- Name: Disease Progression

- Relevance: LOW

- As Found: Unknown

- ID: M21089

- Name: Facies

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14111

- Name: Precancerous Conditions

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000055623

- Term: Keratosis, Actinic

- ID: D000007642

- Term: Keratosis

### Intervention Browse Module - Ancestors

- ID: D000000894

- Term: Anti-Inflammatory Agents, Non-Steroidal

- ID: D000018712

- Term: Analgesics, Non-Narcotic

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000893

- Term: Anti-Inflammatory Agents

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000016861

- Term: Cyclooxygenase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000097912

- Term: Toll-Like Receptor Agonists

- ID: D000091369

- Term: Immunomodulating Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000000276

- Term: Adjuvants, Immunologic

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000007369

- Term: Interferon Inducers

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Analg

- Name: Analgesics

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M1727

- Name: Imiquimod

- Relevance: HIGH

- As Found: Mycophenolate Mofetil

- ID: M7197

- Name: Diclofenac

- Relevance: HIGH

- As Found: Personalized

- ID: M17544

- Name: Vitamin A

- Relevance: LOW

- As Found: Unknown

- ID: M302395

- Name: Retinol palmitate

- Relevance: LOW

- As Found: Unknown

- ID: M4217

- Name: Anti-Inflammatory Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4218

- Name: Anti-Inflammatory Agents, Non-Steroidal

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M20786

- Name: Analgesics, Non-Narcotic

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M19209

- Name: Cyclooxygenase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M3628

- Name: Adjuvants, Immunologic

- Relevance: LOW

- As Found: Unknown

- ID: M10407

- Name: Interferons

- Relevance: LOW

- As Found: Unknown

- ID: T468

- Name: Vitamin A

- Relevance: LOW

- As Found: Unknown

- ID: T462

- Name: Retinol

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000004008

- Term: Diclofenac

- ID: D000077271

- Term: Imiquimod

### Misc Info Module

- Version Holder: 2024-05-24
