Papulopustular Rosacea
Conditions
Keywords
rosacea, papulopustular, azelaic acid, foam
Brief summary
This study will investigate the safety and efficacy of a new formulation of an existing medication for the treatment of papulopustular rosacea. The study will test the active ingredient plus foam against foam alone.
Interventions
Applied topically twice daily for 12 weeks
DRUGVehicle foam
Applied topically twice daily for 12 weeks
Sponsors
Bayer
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * Diagnosis of papulopustular rosacea (IGA score of moderate or severe) with a minimum of 12 and maximum of 50 inflammatory lesions (papules and/or pustules) and persistent erythema with or without telangiectasia * Free of any clinically significant disease which could interfere with the study * Willingness to follow all study procedures * Male or female patient at least 18 years of age
Exclusion criteria
* Subjects known to be non-responders to azelaic acid * Presence of dermatoses that might interfere with the rosacea diagnosis or the evaluation of treatment results * Ocular rosacea, phymatous rosacea * Any condition or therapy that in the opinion of the investigator may pose a risk to the patient of interfere with any evaluation in the study * Facial laser surgery in the 6 weeks prior to the study * Topical or systemic use of prescription or non-prescription medications to treat rosacea * Use of any agent other than the investigational drugs to treat rosacea during the study * Expected use or change in dose in the 90 days prior to the study of beta-blockers, vasodilators, NSAIDs, hormonal treatment or drugs causing acneiform eruptions * Known hypersensitivity to any ingredients of the investigational product formulation * Alcohol or drug abuse * Incapability of giving fully informed consent * Subject is dependent person, i.e., a relative/family member of the investigator and/or is a member of the investigator's staff * Participation in another clinical research study within the last 4 weeks before randomization in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at End of Treatment (LOCF: Last Observation Carried Forward) | At End of treatment (up to 12 weeks) (LOCF) | The IGA is a static evaluation of the overall severity of papulopustular rosacea at a given time. It consists of 5 scores ranging from clear to severe papulopustular rosacea and allows rapid overall evaluation of disease severity: 1) Clear: virtually no rosacea, ie, no papules and/or pustules; no erythema; 2) Minimal: rare papules and/or pustules; residual to mild erythema; 3) Mild: few papules and/or pustules; mild erythema; 4) Moderate: pronounced number of 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. |
| Nominal Change From Baseline in Inflammatory Lesion (IL) Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF) | Baseline and End of treatment (up to 12 weeks) (LOCF) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in IL Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF) | At End of treatment (up to 12 weeks) (LOCF) | — |
| Percentage of Participants With Investigator's Global Assessment (IGA) Based Patient Response at End of Treatment (LOCF) | At End of treatment (up to 12 weeks) (LOCF) | The IGA is a static evaluation of the overall severity of papulopustular rosacea at a given time. It consists of 5 scores ranging from clear to severe papulopustular rosacea and allows rapid overall evaluation of disease severity: 1) Clear: virtually no rosacea, ie, no papules and/or pustules; no erythema; 2) Minimal: rare papules and/or pustules; residual to mild erythema; 3) Mild: few papules and/or pustules; mild erythema; 4) Moderate: pronounced number of papules and/or pustules; moderate erythema; 5) Severe: numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate to severe erythema. Subjects achieving a clear, minimal, or mild IGA at the end of treatment were considered as 'responder'. Subjects with an IGA of moderate or severe at the end of treatment were considered as 'non-responder'. Subjects who prematurely withdraw from study treatment because of lack of efficacy were coded as 'non-responders'. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azelaic Acid Foam, 15% (BAY39-6251) Participants received azelaic acid foam, 15% topically twice daily for 12 weeks | 198 |
| Vehicle Foam Participants received vehicle foam topically twice daily for 12 weeks | 203 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 9 | 13 |
| Overall Study | Protocol Violation | 4 | 2 |
| Overall Study | Reason not known | 4 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 7 |
Baseline characteristics
| Characteristic | Vehicle Foam | Total | Azelaic Acid Foam, 15% (BAY39-6251) |
|---|---|---|---|
| Age, Continuous | 48.9 Years STANDARD_DEVIATION 11.65 | 48.5 Years STANDARD_DEVIATION 11.93 | 48.1 Years STANDARD_DEVIATION 12.23 |
| Investigator's Global Assessment (IGA) score at Baseline | 4.1 Scores on a scale STANDARD_DEVIATION 0.51 | 4.2 Scores on a scale STANDARD_DEVIATION 0.6 | 4.3 Scores on a scale STANDARD_DEVIATION 0.68 |
| Number of inflammatory lesions per participant at Baseline | 20.4 Inflammatory lesions STANDARD_DEVIATION 8.83 | 21.0 Inflammatory lesions STANDARD_DEVIATION 9.38 | 21.6 Inflammatory lesions STANDARD_DEVIATION 9.91 |
| Previous duration of rosacea | 126.3 Months STANDARD_DEVIATION 103.81 | 123.8 Months STANDARD_DEVIATION 108.53 | 121.4 Months STANDARD_DEVIATION 113.38 |
| Sex: Female, Male Female | 143 Participants | 298 Participants | 155 Participants |
| Sex: Female, Male Male | 60 Participants | 103 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 198 | 48 / 203 |
| serious Total, serious adverse events | 1 / 198 | 3 / 203 |
Outcome results
Primary
Nominal Change From Baseline in Inflammatory Lesion (IL) Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF)
Time frame: Baseline and End of treatment (up to 12 weeks) (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azelaic Acid Foam, 15% (BAY39-6251) | Nominal Change From Baseline in Inflammatory Lesion (IL) Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF) | -13.4 Inflammatory lesions | Standard Deviation 10.39 |
| Vehicle Foam | Nominal Change From Baseline in Inflammatory Lesion (IL) Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF) | -9.5 Inflammatory lesions | Standard Deviation 9.73 |
p-value: <0.001ANCOVA
Primary
Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at End of Treatment (LOCF: Last Observation Carried Forward)
The IGA is a static evaluation of the overall severity of papulopustular rosacea at a given time. It consists of 5 scores ranging from clear to severe papulopustular rosacea and allows rapid overall evaluation of disease severity: 1) Clear: virtually no rosacea, ie, no papules and/or pustules; no erythema; 2) Minimal: rare papules and/or pustules; residual to mild erythema; 3) Mild: few papules and/or pustules; mild erythema; 4) Moderate: pronounced number of 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.
Time frame: At End of treatment (up to 12 weeks) (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azelaic Acid Foam, 15% (BAY39-6251) | Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at End of Treatment (LOCF: Last Observation Carried Forward) | 43.4 Percentage of participants |
| Vehicle Foam | Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at End of Treatment (LOCF: Last Observation Carried Forward) | 32.5 Percentage of participants |
p-value: 0.017Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Investigator's Global Assessment (IGA) Based Patient Response at End of Treatment (LOCF)
The IGA is a static evaluation of the overall severity of papulopustular rosacea at a given time. It consists of 5 scores ranging from clear to severe papulopustular rosacea and allows rapid overall evaluation of disease severity: 1) Clear: virtually no rosacea, ie, no papules and/or pustules; no erythema; 2) Minimal: rare papules and/or pustules; residual to mild erythema; 3) Mild: few papules and/or pustules; mild erythema; 4) Moderate: pronounced number of papules and/or pustules; moderate erythema; 5) Severe: numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate to severe erythema. Subjects achieving a clear, minimal, or mild IGA at the end of treatment were considered as 'responder'. Subjects with an IGA of moderate or severe at the end of treatment were considered as 'non-responder'. Subjects who prematurely withdraw from study treatment because of lack of efficacy were coded as 'non-responders'.
Time frame: At End of treatment (up to 12 weeks) (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azelaic Acid Foam, 15% (BAY39-6251) | Percentage of Participants With Investigator's Global Assessment (IGA) Based Patient Response at End of Treatment (LOCF) | 69.2 Percentage of participants |
| Vehicle Foam | Percentage of Participants With Investigator's Global Assessment (IGA) Based Patient Response at End of Treatment (LOCF) | 57.6 Percentage of participants |
Secondary
Percent Change From Baseline in IL Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF)
Time frame: At End of treatment (up to 12 weeks) (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azelaic Acid Foam, 15% (BAY39-6251) | Percent Change From Baseline in IL Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF) | -62.5 Percentage of Inflammatory lesions | Standard Deviation 35.66 |
| Vehicle Foam | Percent Change From Baseline in IL Count (Sum of Papules and Pustules) Per Participant at End of Treatment (LOCF) | -47.8 Percentage of Inflammatory lesions | Standard Deviation 41.28 |