Safety and Efficacy of Azelaic Acid Foam, 15 % in Papulopustular Rosacea

A Randomized, Double-blind, Vehicle-controlled, Multicenter, Parallel-group Clinical Trial to Assess the Safety and Efficacy of Azelaic Acid Foam, 15% Topically Applied Twice Daily for 12 Weeks in Subjects With Papulopustular Rosacea

The purpose of this study is to assess the safety and efficacy of azelaic acid (AzA) foam, 15% topically applied twice daily for 12 weeks in subjects with papulopustular rosacea compared to its vehicle.

Study Overview

• Status: Completed
• Conditions: Papulopustular Rosacea
• Intervention / Treatment: Drug: Azelaic acid foam, 15% (BAY39-6251); Drug: Vehicle foam

Detailed Description

To determine the efficacy of AzA foam, 15% compared to vehicle topically applied twice daily in papulopustular rosacea evaluated by therapeutic success rate according to Investigators Global Assessment (IGA) and change in inflammatory lesion count from baseline to end of treatment.

Evaluation of all adverse events will be covered in Adverse Events section.

• Study Type: Interventional
• Enrollment (Actual): 961
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
    • Birmingham, Alabama, United States, 35233
    • Birmingham, Alabama, United States, 35243
  • California
    • Fremont, California, United States, 94538
    • Los Angeles, California, United States, 90045
    • Sacramento, California, United States, 95816
    • San Diego, California, United States, 92103
    • San Francisco, California, United States, 94143-0660
    • Santa Ana, California, United States, 92705
    • Santa Monica, California, United States, 90404
  • Colorado
    • Colorado Springs, Colorado, United States, 80915
  • Florida
    • Boynton Beach, Florida, United States, 33437
    • Boynton Beach, Florida, United States, 33472-2952
    • Jacksonville, Florida, United States, 32258
    • Miami, Florida, United States, 33144
    • Miami, Florida, United States, 33175
    • Miramar, Florida, United States, 33027
    • Ormond Beach, Florida, United States, 32174
    • Saint Augustine, Florida, United States, 32086
  • Illinois
    • Buffalo Grove, Illinois, United States, 60089
    • Chicago, Illinois, United States, 60625
  • Indiana
    • Plainfield, Indiana, United States, 46168
  • Kentucky
    • Louisville, Kentucky, United States, 40202
    • Richmond, Kentucky, United States, 40475
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
  • Michigan
    • Warren, Michigan, United States, 48088
    • West Bloomfield, Michigan, United States, 48322
  • Minnesota
    • Fridley, Minnesota, United States, 55432
  • Missouri
    • Saint Louis, Missouri, United States, 63141
  • Nebraska
    • Omaha, Nebraska, United States, 68144
  • Nevada
    • Las Vegas, Nevada, United States, 89128
    • Las Vegas, Nevada, United States, 89144
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
  • New York
    • New York, New York, United States, 10029
    • Stony Brook, New York, United States, 11790
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
    • Hickory, North Carolina, United States, 28602
    • High Point, North Carolina, United States, 27262
    • Raleigh, North Carolina, United States, 27612
    • Winston-Salem, North Carolina, United States, 27103
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
  • South Carolina
    • Anderson, South Carolina, United States, 29621
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
  • Texas
    • Austin, Texas, United States, 78759
    • Plano, Texas, United States, 75093
    • Webster, Texas, United States, 77598
  • Utah
    • Salt Lake City, Utah, United States, 84117
  • Washington
    • Seattle, Washington, United States, 98101
    • Spokane, Washington, United States, 99204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of papulopustular rosacea
• Free of any clinically significant disease, which could interfere with the study
• Male or female subject aged ≥ 18 years
• Willingness of subject to follow all study procedures
• Signed written informed consent before any study-related activities are carried out

Exclusion Criteria:

• Subjects who are known to be non-responders to azelaic acid
• Presence of dermatoses that might interfere with rosacea diagnosis
• Ocular rosacea; phymatous rosacea; subjects with plaque-type rosacea lesions, papulopustular rosacea that requires systemic treatment
• Topical use of any prescription or non-prescription medication to treat rosacea within 6 weeks prior to randomization and throughout the study
• Systemic use of any prescription or non-prescription medication to treat rosacea (Retinoids within 6 months, Tetracycline within 2 months, Corticosteroids, erythromycin, azithromycin, and/or metronidazole within 4 weeks) prior to randomization and throughout the study
• Facial laser surgery for telangiectasia (or other conditions) within 6 weeks prior to randomization
• Known hypersensitivity to any ingredients of the investigational product formulation
• Participation in another clinical research in parallel or within the last 4 weeks before randomization in this study
• Any condition or therapy that in the investigator's opinion may pose a risk to the subject or that could interfere with any evaluation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azelaic acid foam, 15% (BAY39-6251); 0.5 g azelaic acid (AzA) foam, 15% applied twice daily (BID) topical and nonocclusive on facial skin for 12 weeks.	Drug: Azelaic acid foam, 15% (BAY39-6251); Azelaic acid twice daily topical application
Placebo Comparator: Vehicle foam; 0.5 g vehicle foam applied twice daily topical and nonocclusive on facial skin for 12 weeks.	Drug: Vehicle foam; twice daily topical application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at End of Treatment (LOCF: Last Observation Carried Forward)	Static evaluation of overall severity of papulopustular rosacea at a given time: 1) Clear: no papules and/or pustules; no erythema; 2) Minimal: rare papules and/or pustules; faint up to but not including mild erythema; 3) Mild: few papules and/or pustules; mild erythema; 4) Moderate: pronounced number of papules and/or pustules (but less than numerous papules and/or pustules); moderate erythema; 5) Severe: numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate to severe erythema. Therapeutic success is defined as an IGA score of clear or minimal.	At end of treatment (LOCF), up to 12 weeks
Nominal Change From Baseline in Inflammatory Lesion (IL) Count at End of Treatment (LOCF)	The mean (standard deviation) change from baseline in the inflammatory lesion count at the end of treatment is provided.	Baseline and end of treatment (LOCF), up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Inflammatory Lesion Count at End of Treatment (LOCF)	The mean (standard deviation) percentage change in inflammatory lesion count from baseline to end of study is provided.	Baseline and end of treatment (LOCF), up to 12 weeks
Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Response at End of Treatment (LOCF)	Participants achieving a clear, minimal, or mild IGA at the end of treatment were considered as 'responder'. Participants with an IGA of moderate or severe at the end of treatment were considered as 'non-responder'. Participants who prematurely withdraw from study treatment because of lack of efficacy were coded as 'non-responders'. The percentage of responders is presented.	At end of treatment (LOCF), up to 12 weeks
Grouped Changes From Baseline in Erythema Intensity Score at End of Treatment (LOCF)	Erythema was rated as: clear or almost clear; mild; moderate; or severe. For the assessment of the grouped change in erythema ratings, the baseline examination was used to group into 'improved', 'no change', or 'worsened'. A participant was considered to have an 'improved' erythema rating if the erythema rating was lower compared to the baseline rating, 'no change' if the rating was identical, and 'worsened' if the rating was higher. The percentage of participants in each of these categories is presented.	Baseline and end of treatment (LOCF), up to 12 weeks
Percentage of Participants With Investigator's Global Assessment (IGA) Scores at End of Treatment (LOCF)	The IGA consists of 5 scores: 1) Clear: no papules and/or pustules; no erythema; 2) Minimal: rare papules and/or pustules; faint up to but not including mild erythema; 3) Mild: few papules and/or pustules; mild erythema; 4) Moderate: pronounced number of papules and/or pustules (but less than numerous papules and/or pustules); moderate erythema; 5) Severe: numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate to severe erythema. The percentage of participants with each score at the end of treatment is provided.	At end of treatment (LOCF), up to 12 weeks
Nominal Value of Inflammatory Lesion Count at End of Treatment (LOCF)	The mean (standard deviation) lesion count at the end of treatment is provided.	At end of treatment (LOCF), up to 12 weeks
Percentage of Participants With Erythema Intensity Score at End of Treatment (LOCF)	The percentage of participants in each rating category of erythema (clear or almost clear; mild; moderate; severe) at the end of treatment is provided.	At end of treatment (LOCF), up to 12 weeks
Grouped Changes From Baseline in Telangiectasia Intensity Score at End of Treatment (LOCF)	Telangiectasia was rated as: no; mild; moderate; or severe. At the end of study, a participant was considered to have an 'improved' telangiectasia rating if the telangiectasia rating was lower compared to the baseline rating, 'no change' if the rating was identical, and 'worsened' if the rating was higher. The percentage of participants in each category is presented.	Baseline and end of treatment (LOCF), up to 12 weeks
Percentage of Participants With Facial Skin Color Rating at End of Treatment (LOCF)	Facial skin color (as compared with skin outside the treatment area) was rated as: normal; barely visible skin lightening; mild skin lightening; moderate skin lightening; severe skin lightening. The percentage of participants in each category of facial skin color at the end of study is presented.	At end of treatment (LOCF), up to 12 weeks
Participants' Global Assessment of Treatment Response at End of Treatment	At the end of treatment, participants assessed the change of papulopustular rosacea from baseline (how it looked, felt, appeared to others) as excellent improvement, good improvement, fair improvement, no improvement, or worse. The number of participants in each category of this assessment is presented.	At end of treatment, up to 12 weeks
Participants' Global Assessment of Tolerability at End of Treatment	At the end of treatment, participants provided their opinion on local tolerability of the investigational product as excellent, good, acceptable despite minor irritation, less acceptable due to continuous irritation, non-acceptable, or no opinion. The number of participants in each category of this assessment is presented.	At end of treatment, up to 12 weeks
Participants' Opinion on Cosmetic Acceptability at End of Treatment	At the end of treatment, participants provided their opinion on cosmetic acceptability of the investigational product as very good, good, satisfactory, poor, or no opinion. The number of participants in each category of this assessment is presented.	At end of treatment, up to 12 weeks
Participants' Opinion on Practicability of Product Use in Facial Areas Next to the Hairline at End of Treatment	At the end of treatment, participants provided their opinion on the practicability of the use of the investigational product in facial areas next to the hairline as very good, good, satisfactory, poor, or no opinion. The number of participants in each category of this assessment is presented.	At end of treatment, up to 12 weeks
Change From Baseline in Rosacea Quality of Life (RosaQoL) Questionnaire at End of Treatment - Overall Quality of Life Score	The Rosacea Quality of Life (RosaQoL) is a questionnaire to evaluate the effect of rosacea on a participant's quality of life. Each of the 21 items in this questionnaire asks about the frequency with which a particular aspect of living with rosacea affects the participant: possible responses for each item are "never" (score=1), "rarely" (score=2), "sometimes" (score=3), "often" (score=4), or "all the time" (score=5). The overall score is the sum of the results from all 21 questions, with possible scores ranging from 21 (best) to 105 (worst); the higher the score, the more quality of life is impaired. The mean (standard deviation) of the change, defined as end of treatment overall score minus baseline overall score, is presented.	Baseline and end of treatment, up to 12 weeks
Number of Participants With Change From Baseline in Dermatology Life Quality Index (DLQI) Questionnaire at End of Treatment - Overall Score	The Dermatology Life Quality Index (DLQI) is a questionnaire consisting of a set of 10 questions that evaluate the degree to which the participant's skin has affected certain behaviors and quality of life over the past week. Possible responses to each question are: "very much" (question 7: "yes") (score=3), "a lot" (score=2), "a little" (score=1), or "not at all"/"not relevant" (score=0). The DLQI overall score is the sum of the results from all 10 questions, with possible scores ranging from 0 (best) to 30 (worst); the higher the score, the more quality of life is impaired. The number of participants with score changes (end of treatment - baseline) in DLQI overall score from baseline to end of treatment <=-5 and >-5 are presented.	Baseline and end of treatment, up to 12 weeks
Change From Baseline in EuroQol Group Questionnaire-Visual Analogue Scale (EQ-VAS) at End of Treatment	The EuroQol Group Questionnaire-Visual Analogue Scale (EQ-VAS) is a standardized instrument for use as a measure of health outcome. The EQ-VAS asks for a judgment of the overall health status assessed by the participant her/himself. The 20-cm visual analog scale (VAS) has endpoints labeled "best imaginable health state" and "worst imaginable health state" that are anchored at 100 and 0, respectively. Respondents are asked to indicate how they rate their own health by drawing a line from an anchor box to that point on the EQ-VAS, which best represents their own health on that day; higher scores indicate a better health state. The median (range) of the change, defined as EQ-VAS at end of treatment minus EQ-VAS at baseline, is presented.	Baseline and end of treatment, up to 12 weeks
Change From Baseline in Index Value at End of Treatment	The EuroQol Group Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) is a standardized instrument for use as a measure of health outcome. Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status. It is used to assess the level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each dimension is evaluated using 5 levels: "no problems" (level 1), "slight problems" (level 2), "moderate problems" (level 3), "severe problems" (level 4), and "extreme problems" (level 5). A scoring formula developed by EuroQol Group calculates a single index value from the results from all 5 domains along a continuum of 0 (death) to 1 (full health). The median (range) change, defined as the index value at end of treatment minus the index value at baseline, is presented.	Baseline and end of treatment, up to 12 weeks

Collaborators and Investigators

• Sponsor: LEO Pharma
• Collaborators: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Draelos ZD, Elewski BE, Harper JC, Sand M, Staedtler G, Nkulikiyinka R, Shakery K. A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea. Cutis. 2015 Jul;96(1):54-61.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 13, 2012
• First Posted (Estimated): March 15, 2012

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Rosacea
• Additional Relevant MeSH Terms: Skin Diseases; Rosacea; Antineoplastic Agents; Dermatologic Agents; Azelaic acid
• Other Study ID Numbers: 16080; 1401846 (Other Identifier: Company Internal)