Atralin Gel for the Treatment of Rosacea

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

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).

Study Overview

• Status: Terminated
• Conditions: Rosacea
• Intervention / Treatment: Drug: vehicle gel; Drug: Atralin gel

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects 18 years of age and older of any race.
2. Clinical diagnosis of mild to moderate erythematotelangiectatic facial rosacea based on physician evaluation.
3. Willing and able to understand and sign informed consent.
4. Able to complete study and comply with study procedures.

Exclusion Criteria:

1. Severe self reported facial sensitivity
2. History of allergy to fish
3. Severe sun sensitivity
4. Severe erythematotelangiectatic rosacea requiring systemic treatment
5. Papulopustular, Ocular-only, Phymatous rosacea, Steroid rosacea, pyoderma faciale
6. Unwilling to undergo facial biopsies
7. Concomitant use of medications that are reported to exacerbate rosacea, such as topical and systemic steroids
8. Use of topical rosacea treatments in the past 2 weeks.
9. Use of systemic antibiotics in the past 4 weeks.
10. Use of systemic retinoids within the past 6 months.
11. Use of topical retinoids within the past 3 months
12. Use of laser or light based rosacea treatments within the past 2 months.
13. Cosmetic procedures (e.g., superficial chemical peels, exfoliation or microdermabrasion of the face) within the past two months
14. Use of topical anti-aging medications including alpha hydroxy acids, salicylic acid, beta-hydroxy acid, vitamin A, vitamin E, ascorbic acid
15. Other dermatologic conditions that require the use of interfering topical or systemic therapy or that might interfere with study assessments.
16. 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.
17. 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).
18. Subjects who are lactating.
19. Use of any investigational therapy within the past 4 weeks.
20. Known hypersensitivity or previous allergic reaction to retinoids
21. Carcinoid, Pheochromocytoma or other systemic flushing causes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Vehicle gel; 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; 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.
ACTIVE_COMPARATOR: Atralin gel; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lisa E. Maier
• Collaborators: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Lisa E Maier, M.D., University of Michigan

Publications and helpful links

General Publications

• Pelle MT, Crawford GH, James WD. Rosacea: II. Therapy. J Am Acad Dermatol. 2004 Oct;51(4):499-512; quiz 513-4. doi: 10.1016/j.jaad.2004.03.033.
• Ertl GA, Levine N, Kligman AM. A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Arch Dermatol. 1994 Mar;130(3):319-24.
• Vienne MP, Ochando N, Borrel MT, Gall Y, Lauze C, Dupuy P. Retinaldehyde alleviates rosacea. Dermatology. 1999;199 Suppl 1:53-6. doi: 10.1159/000051380.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): January 1, 2013

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 18, 2010
• First Posted (ESTIMATE): May 19, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 16, 2014
• Last Update Submitted That Met QC Criteria: July 15, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: rosacea; tretinoin; atralin
• Additional Relevant MeSH Terms: Skin Diseases; Rosacea; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: Derm 616