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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Papulopustular Rosacea

Intervention / Treatment
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* Drug: Azelaic acid foam, 15% (BAY39-6251)
* Drug: Vehicle foam


Participation Criteria
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Eligibility Criteria
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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

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: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rosacea