Atralin Gel for the Treatment of Rosacea

Study Overview
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Brief Summary
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Erythematotelangiectatic rosacea is a type of rosacea that causes a red face often with frequent flushing, topical sensitivity and prominent blood vessels. We think that long term damage to skin from the sun (photodamage) may play a role in causing this type of rosacea. Tretinoin is a topical medication that is known to improve photodamage. We want to find out if Atralin (tretinoin 0.05%) Gel used for up to 46 weeks will improve erythematotelangiectatic rosacea (ETR).

Official Title
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Investigation of the Topical Retinoid, Atralin Gel 0.05% for the Treatment of Erythematotelangiectatic Rosacea

Conditions
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Rosacea

Intervention / Treatment
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* Drug: vehicle gel
* Drug: Atralin gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 18 years of age and older of any race. Clinical diagnosis of mild to moderate erythematotelangiectatic facial rosacea based on physician evaluation. Willing and able to understand and sign informed consent. Able to complete study and comply with study procedures. Exclusion Criteria: Severe self reported facial sensitivity History of allergy to fish Severe sun sensitivity Severe erythematotelangiectatic rosacea requiring systemic treatment Papulopustular, Ocular-only, Phymatous rosacea, Steroid rosacea, pyoderma faciale Unwilling to undergo facial biopsies Concomitant use of medications that are reported to exacerbate rosacea, such as topical and systemic steroids Use of topical rosacea treatments in the past 2 weeks. Use of systemic antibiotics in the past 4 weeks. Use of systemic retinoids within the past 6 months. Use of topical retinoids within the past 3 months Use of laser or light based rosacea treatments within the past 2 months. Cosmetic procedures (e.g., superficial chemical peels, exfoliation or microdermabrasion of the face) within the past two months Use of topical anti-aging medications including alpha hydroxy acids, salicylic acid, beta-hydroxy acid, vitamin A, vitamin E, ascorbic acid Other dermatologic conditions that require the use of interfering topical or systemic therapy or that might interfere with study assessments. Clinically significant abnormal findings or conditions (other than rosacea), which might, in the opinion of the Investigator, interfere with study evaluations or pose a risk to subject safety during the study. If female, Subjects who are either of non-child bearing potential (defined as postmenopausal -absence of menstrual bleeding for 1 year - or as having undergone bilateral tubal ligation, hysterectomy or bilateral ovariectomy) or, if of childbearing potential, Subjects who have had a negative urine pregnancy test at the beginning of the study, and have agreed to practice appropriate birth-control to prevent pregnancy during the study.(The type and dose of birth control must have been stable for at least 2 months prior to study entry and not be expected to change during the study). Subjects who are lactating. Use of any investigational therapy within the past 4 weeks. Known hypersensitivity or previous allergic reaction to retinoids Carcinoid, Pheochromocytoma or other systemic flushing causes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle gel<br>Topical gel that does not contain active drug. The gel will be applied initially 3 times per week to the face. If no irritation seen at follow up visit, the investigator will consider increasing the frequency of use. This topical medication will not be applied more than once daily. If there is irritation, the subject will be asked to decrease frequency of use. | Drug: vehicle gel<br>* Topical gel that does not contain active drug. The gel will be applied initially 3 times per week to the face. If no irritation seen at follow up visit, the investigator will consider increasing the frequency of use. This topical medication will not be applied more than once daily. If there is irritation, the subject will be asked to decrease frequency of use.<br>|
| Active Comparator: Atralin gel<br>Topical Atralin gel will be applied initially 3 times per week to the face. If no irritation seen at follow up visit, the investigator will consider increasing the frequency of use. This topical medication will not be applied more than once daily. If there is irritation, the subject will be asked to decrease frequency of use. This drug will be used for the duration of the study. | Drug: Atralin gel<br>* Topical Atralin gel will be applied initially 3 times per week to the face. If no irritation seen at follow up visit, the investigator will consider increasing the frequency of use. This topical medication will not be applied more than once daily. If there is irritation, the subject will be asked to decrease frequency of use. This drug will be used for the duration of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Erythematotelangiectatic Rosacea Signs: Redness (Non Transient Erythema) | Severity of erythematotelangiectatic rosacea signs will be measured by taking into account the following: redness, telangiectasia, facial edema, dry skin | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Signs: Telangiectasia | Severity of erythematotelangiectatic rosacea signs will be measured by taking into account the following: redness, telangiectasia, facial edema, dry skin | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Signs: Facial Edema | Severity of erythematotelangiectatic rosacea signs will be measured by taking into account the following: redness, telangiectasia, facial edema, dry skin | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Signs: Dry Skin | Severity of erythematotelangiectatic rosacea signs will be measured by taking into account the following: redness, telangiectasia, facial edema, dry skin | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Presence of Flushing | Flushing is defined as a temporary redness of the face, neck and chest. Subjects were asked to choose the best answer that applied to them in response to the questions Do you have flushing?. | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Facial Burning | Severity of erythematotelangiectatic rosacea symptoms was assessed by asking subjects to rate the facial burning feature of their rosacea. | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Facial Stinging | Severity of erythematotelangiectatic rosacea symptoms was assessed by asking subjects to rate the Facial Stinging feature of their rosacea. | 24 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Assessment of Product | Severity of erythematotelangiectatic rosacea symptoms was assessed by asking subjects to give an overall self-assessment of product tolerance. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | The Dermatology Life Quality Index (DLQI) questionnaire was given at each visit. It involves 10 questions that relate to symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. The total DLQI score is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | 2, 6, 12, 18, 24 weeks | 
| Photodamage | Photodamage was measured at baseline and Week 24 visits using the nine point Hamilton-Griffiths Photoaging Score categories. The categories were developed using photographs of subject representing grades of photodamge from none (0) to severe (8). A direct comparison is made between the subject and the photographic standards. If an exact match cannot be made, the interstandard scores (1, 3, 5, 7) are used. | 24 weeks | 
| Signs of Other Rosacea Subtypes: Ocular Manifestations of Rosacea | Signs of other rosacea subtypes using rosacea clinical scores: ocular manifestations of rosacea | 2, 6, 12, 18 and 24 weeks | 
| Signs of Other Rosacea Subtypes: Phymatous Changes of Rosacea | Signs of other rosacea subtypes using rosacea clinical scores: phymatous changes of rosacea | 2, 6, 12, 18 and 24 weeks | 
| Signs of Other Rosacea Subtypes: Papulopustular | Signs of other rosacea subtypes includes papulopustular, inflammatory papule count | 2, 6, 12, 18, 24 weeks | 
| Molecular Markers of Inflammation | These will be evaluated from skin biopsies from some subjects at baseline and final evaluation at 24 weeks. Gene expression data were normalized and presented as fold change from baseline to week 24 visit. Markers of inflammation include Tachykinin 1 (TAC1), CXC Motif Receptor 4 (CXCR4), CXC Motif Ligand 12 (CXCL12), and Tumor Necrosis Factor Alpha (TNFa). | 24 weeks | 
| Molecular Evidence of Photodamage | These will be evaluated from skin biopsies from some subjects at baseline and final evaluation at 24 weeks. Gene expression data were normalized and presented as fold change from baseline to week 24 visit. Markers of photodamage include Collagen 1 (COL-1), Collagen 3 (COL-3), Matrix Metalloproteinase 1 (MMP1), Matrix Metalloproteinase 3 (MMP3), and Matrix Metalloproteinase 9 (MMP9). | 24 weeks | 
| Severity of Erythematotelangiectatic Signs: Non-Transient Erythema (Redness) | Severity of erythematotelangiectatic signs include redness (non-transient erythema), telangiectasia, facial edema, and dry skin. | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Signs: Telangiectasia | Severity of erythematotelangiectatic signs include redness (non-transient erythema), telangiectasia, facial edema, and dry skin. | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Signs: Facial Edema | Severity of erythematotelangiectatic signs include redness (non-transient erythema), telangiectasia, facial edema, and dry skin. | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Signs: Dryness/Irritation | Severity of erythematotelangiectatic signs include redness (non-transient erythema), telangiectasia, facial edema, and dry skin. | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Presence of Flushing | Evaluation of erythematotelangiectatic rosacea symptoms includes subject reporting of flushing, burning, stinging, topical product intolerance | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Facial Burning | Evaluation of erythematotelangiectatic rosacea symptoms includes subject reporting of flushing, burning, stinging, topical product intolerance | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Facial Stinging | Evaluation of erythematotelangiectatic rosacea symptoms includes subject reporting of flushing, burning, stinging, topical product intolerance | 2, 6, 12, 18 weeks | 
| Severity of Erythematotelangiectatic Rosacea Symptoms: Self-Reported Product Assessment | Evaluation of erythematotelangiectatic rosacea symptoms includes subject reporting of flushing, burning, stinging, topical product intolerance | 2, 6, 12, 18 weeks | 
| Skin Irritation Assessed by Facial Stinging Upon Product Application |  | 2, 6, 12, 18 weeks | 
| Skin Irritation Assessed by Facial Itching Upon Product Application |  | 2, 6, 12, 18 weeks | 
| Skin Irritation Assessed by Facial Burning Upon Product Application |  | 2, 6, 12, 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rosacea, tretinoin, atralin