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

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01025635
• Collaborator: Bayer (Industry)
• Enrollment: 401
• Locations: 20
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 20.1
• Patients Per Site Per Month: 2.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Papulopustular Rosacea	Drug: Azelaic acid foam 15%; Drug: Vehicle foam	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 401 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Vehicle-controlled, Multicenter, Parallel-group Study to Investigate Safety and Efficacy of Azelaic Acid Foam, 15% Topically Applied Twice Daily in Subjects With Papulopustular Rosacea
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azelaic acid foam, 15% (BAY39-6251) Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Drug: Azelaic acid foam 15%; Applied topically twice daily for 12 weeks
Placebo Comparator: Vehicle foam Participants received vehicle foam topically twice daily for 12 weeks	Drug: Vehicle foam; Applied topically twice daily for 12 weeks

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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)]

2. 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'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35209
2		Birmingham	Alabama	United States	35233
3		Fremont	California	United States	94538
4		Santa Monica	California	United States	90404
5		Miami	Florida	United States	33175
6		Miramar	Florida	United States	33027
7		Omaha	Nebraska	United States	68144
8		Albuquerque	New Mexico	United States	87106
9		High Point	North Carolina	United States	27262
10		Wilmington	North Carolina	United States	28401
11		Winston-Salem	North Carolina	United States	27103
12		Portland	Oregon	United States	97210
13		Johnston	Rhode Island	United States	02919
14		Simpsonville	South Carolina	United States	29681
15		Knoxville	Tennessee	United States	37922
16		Nashville	Tennessee	United States	37215
17		Austin	Texas	United States	78759
18		Plano	Texas	United States	75093
19		Salt Lake City	Utah	United States	84124
20		Madison	Wisconsin	United States	53719

Sponsors and Collaborators

• LEO Pharma
• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

• Draelos ZD, Elewski B, Staedtler G, Havlickova B. Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study. Cutis. 2013 Dec;92(6):306-17.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT01025635
• Other Study ID Numbers: 14955; 1403120
• First Posted: Dec 3, 2009
• Last Update Posted: Mar 31, 2020
• Last Verified: Apr 1, 2014

• Keywords provided by LEO Pharma: rosacea; papulopustular; azelaic acid; foam
• Additional relevant MeSH terms: Rosacea; Azelaic acid

Study Results

Participant Flow

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)	Vehicle Foam
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Participants received vehicle foam topically twice daily for 12 weeks
Period Title: Overall Study
STARTED	198	203
COMPLETED	175	178
NOT COMPLETED	23	25

Baseline Characteristics

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)	Vehicle Foam	Total
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Participants received vehicle foam topically twice daily for 12 weeks	Total of all reporting groups
Overall Participants	198	203	401
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.1 (12.23)	48.9 (11.65)	48.5 (11.93)
Sex: Female, Male (Count of Participants)
Female	155 78.3%	143 70.4%	298 74.3%
Male	43 21.7%	60 29.6%	103 25.7%
Previous duration of rosacea (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	121.4 (113.38)	126.3 (103.81)	123.8 (108.53)
Investigator's Global Assessment (IGA) score at Baseline (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	4.3 (0.68)	4.1 (0.51)	4.2 (0.60)
Number of inflammatory lesions per participant at Baseline (Inflammatory lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Inflammatory lesions]	21.6 (9.91)	20.4 (8.83)	21.0 (9.38)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at End of Treatment (LOCF: Last Observation Carried Forward)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)	Vehicle Foam
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Participants received vehicle foam topically twice daily for 12 weeks
Measure Participants	198	203
Number [Percentage of participants]	43.4 21.9%	32.5 16%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azelaic Acid Foam, 15% (BAY39-6251), Vehicle Foam
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	study center adjusted

2. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)	Vehicle Foam
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Participants received vehicle foam topically twice daily for 12 weeks
Measure Participants	198	203
Mean (Standard Deviation) [Inflammatory lesions]	-13.4 (10.39)	-9.5 (9.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azelaic Acid Foam, 15% (BAY39-6251), Vehicle Foam
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	with factors treatment group, study center, and baseline lesion count as covariate

3. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)	Vehicle Foam
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Participants received vehicle foam topically twice daily for 12 weeks
Measure Participants	198	203
Mean (Standard Deviation) [Percentage of Inflammatory lesions]	-62.5 (35.66)	-47.8 (41.28)

4. Secondary Outcome

Title	Percentage of Participants With Investigator's Global Assessment (IGA) Based Patient Response at End of Treatment (LOCF)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)	Vehicle Foam
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks	Participants received vehicle foam topically twice daily for 12 weeks
Measure Participants	198	203
Number [Percentage of participants]	69.2 34.9%	57.6 28.4%

Adverse Events

Arm/Group Title	Azelaic Acid Foam, 15% (BAY39-6251)		Vehicle Foam
Arm/Group Description	Participants received azelaic acid foam, 15% topically twice daily for 12 weeks		Participants received vehicle foam topically twice daily for 12 weeks
All Cause Mortality
	Azelaic Acid Foam, 15% (BAY39-6251)		Vehicle Foam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Azelaic Acid Foam, 15% (BAY39-6251)		Vehicle Foam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/198 (0.5%)		3/203 (1.5%)
Infections and infestations
Cellulitis	1/198 (0.5%)	1	0/203 (0%)	0
Injury, poisoning and procedural complications
Concussion	0/198 (0%)	0	1/203 (0.5%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/198 (0%)	0	1/203 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer	0/198 (0%)	0	1/203 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Azelaic Acid Foam, 15% (BAY39-6251)		Vehicle Foam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/198 (34.3%)		48/203 (23.6%)
Ear and labyrinth disorders
Vertigo	1/198 (0.5%)	1	0/203 (0%)	0
Endocrine disorders
Hypothyroidism	0/198 (0%)	0	1/203 (0.5%)	1
Gastrointestinal disorders
Abdominal discomfort	1/198 (0.5%)	1	0/203 (0%)	0
Constipation	1/198 (0.5%)	1	0/203 (0%)	0
Diarrhoea	2/198 (1%)	2	0/203 (0%)	0
Food poisoning	1/198 (0.5%)	1	0/203 (0%)	0
Gastritis	1/198 (0.5%)	1	0/203 (0%)	0
Nausea	3/198 (1.5%)	3	1/203 (0.5%)	1
Toothache	1/198 (0.5%)	1	1/203 (0.5%)	1
Vomiting	1/198 (0.5%)	1	0/203 (0%)	0
Abdominal hernia	0/198 (0%)	0	1/203 (0.5%)	1
General disorders
Application site erythema	0/198 (0%)	0	1/203 (0.5%)	1
Application site pain	9/198 (4.5%)	9	3/203 (1.5%)	4
Application site pruritus	3/198 (1.5%)	3	0/203 (0%)	0
Chest pain	0/198 (0%)	0	2/203 (1%)	2
Cyst	1/198 (0.5%)	1	0/203 (0%)	0
Feeling hot	0/198 (0%)	0	1/203 (0.5%)	1
Oedema peripheral	1/198 (0.5%)	1	0/203 (0%)	0
Pain	7/198 (3.5%)	7	1/203 (0.5%)	1
Pyrexia	0/198 (0%)	0	1/203 (0.5%)	1
Swelling	0/198 (0%)	0	1/203 (0.5%)	1
Tenderness	1/198 (0.5%)	2	0/203 (0%)	0
Application site dryness	0/198 (0%)	0	1/203 (0.5%)	1
Application site paraesthesia	2/198 (1%)	2	1/203 (0.5%)	1
Infections and infestations
Bronchitis	3/198 (1.5%)	3	0/203 (0%)	0
Fungal infection	0/198 (0%)	0	1/203 (0.5%)	1
Gastroenteritis viral	0/198 (0%)	0	1/203 (0.5%)	1
Influenza	0/198 (0%)	0	1/203 (0.5%)	1
Lower respiratory tract infection	0/198 (0%)	0	1/203 (0.5%)	1
Nasopharyngitis	7/198 (3.5%)	7	6/203 (3%)	6
Pharyngitis streptococcal	0/198 (0%)	0	2/203 (1%)	2
Rhinitis	0/198 (0%)	0	1/203 (0.5%)	1
Sinusitis	2/198 (1%)	2	2/203 (1%)	2
Upper respiratory tract infection	2/198 (1%)	2	3/203 (1.5%)	4
Urinary tract infection	2/198 (1%)	2	0/203 (0%)	0
Viral upper respiratory tract infection	2/198 (1%)	2	0/203 (0%)	0
Lymph gland infection	0/198 (0%)	0	1/203 (0.5%)	1
Staphylococcal infection	0/198 (0%)	0	1/203 (0.5%)	1
Vulvovaginal mycotic infection	1/198 (0.5%)	1	0/203 (0%)	0
Oral herpes	1/198 (0.5%)	1	0/203 (0%)	0
Gastrointestinal viral infection	1/198 (0.5%)	1	0/203 (0%)	0
Injury, poisoning and procedural complications
Sternal fracture	0/198 (0%)	0	1/203 (0.5%)	1
Sunburn	2/198 (1%)	2	0/203 (0%)	0
Whiplash injury	1/198 (0.5%)	1	0/203 (0%)	0
Excoriation	1/198 (0.5%)	2	0/203 (0%)	0
Muscle strain	0/198 (0%)	0	1/203 (0.5%)	1
Contusion	1/198 (0.5%)	1	0/203 (0%)	0
Skin laceration	1/198 (0.5%)	2	1/203 (0.5%)	1
Procedural pain	0/198 (0%)	0	1/203 (0.5%)	1
Ligament rupture	1/198 (0.5%)	1	0/203 (0%)	0
Investigations
Blood pressure increased	1/198 (0.5%)	1	1/203 (0.5%)	1
Heart rate irregular	0/198 (0%)	0	1/203 (0.5%)	1
Metabolism and nutrition disorders
Gout	1/198 (0.5%)	1	0/203 (0%)	0
Hypercholesterolaemia	0/198 (0%)	0	1/203 (0.5%)	1
Hypoglycaemia	1/198 (0.5%)	1	0/203 (0%)	0
Vitamin D deficiency	0/198 (0%)	0	1/203 (0.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/198 (0.5%)	1	0/203 (0%)	0
Back pain	0/198 (0%)	0	3/203 (1.5%)	3
Exostosis	1/198 (0.5%)	1	0/203 (0%)	0
Myalgia	0/198 (0%)	0	1/203 (0.5%)	1
Osteoarthritis	0/198 (0%)	0	1/203 (0.5%)	1
Muscle tightness	0/198 (0%)	0	1/203 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/198 (0%)	0	1/203 (0.5%)	2
Nervous system disorders
Burning sensation	3/198 (1.5%)	3	0/203 (0%)	0
Headache	9/198 (4.5%)	21	2/203 (1%)	3
Nerve compression	1/198 (0.5%)	1	0/203 (0%)	0
Paraesthesia	1/198 (0.5%)	1	0/203 (0%)	0
Sciatica	0/198 (0%)	0	1/203 (0.5%)	1
Tension headache	0/198 (0%)	0	1/203 (0.5%)	1
Psychiatric disorders
Insomnia	1/198 (0.5%)	1	0/203 (0%)	0
Reproductive system and breast disorders
Ovarian cyst	1/198 (0.5%)	1	0/203 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/198 (1%)	2	1/203 (0.5%)	1
Nasal congestion	3/198 (1.5%)	3	2/203 (1%)	2
Sinus congestion	1/198 (0.5%)	1	1/203 (0.5%)	1
Wheezing	0/198 (0%)	0	1/203 (0.5%)	1
Nasal disorder	0/198 (0%)	0	1/203 (0.5%)	1
Oropharyngeal pain	2/198 (1%)	2	1/203 (0.5%)	1
Skin and subcutaneous tissue disorders
Actinic keratosis	0/198 (0%)	0	1/203 (0.5%)	1
Dermal cyst	0/198 (0%)	0	1/203 (0.5%)	1
Dermatitis contact	0/198 (0%)	0	1/203 (0.5%)	2
Dry skin	0/198 (0%)	0	1/203 (0.5%)	1
Eczema asteatotic	1/198 (0.5%)	1	0/203 (0%)	0
Erythema	1/198 (0.5%)	1	1/203 (0.5%)	1
Pruritus	4/198 (2%)	4	0/203 (0%)	0
Rash morbilliform	1/198 (0.5%)	1	0/203 (0%)	0
Rosacea	1/198 (0.5%)	1	0/203 (0%)	0
Skin lesion	1/198 (0.5%)	1	0/203 (0%)	0
Telangiectasia	0/198 (0%)	0	1/203 (0.5%)	1
Urticaria	1/198 (0.5%)	2	0/203 (0%)	0
Surgical and medical procedures
Dental care	1/198 (0.5%)	1	0/203 (0%)	0
Mammoplasty	1/198 (0.5%)	1	0/203 (0%)	0
Vascular disorders
Flushing	0/198 (0%)	0	1/203 (0.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator may publish the results of Study only after review, comment and approval by Intendis. At least sixty (60) days prior to submitting a manuscript to a publisher or other outside persons (i.e., reviewer(s)) or prior to any public presentation), a copy of the manuscript or presentation will be provided to Intendis by the Investigator for review and comment. No publication of confidential information shall be made without Intendis' prior written consent.