Efficacy of Topical Azelaic Acid 15% Gel Plus Anti-inflammatory Dose Doxycycline or Metronidazole Gel 1% Plus Anti-inflammatory Dose Doxycycline in Moderate Papulopustular Rosacea

• ClinicalTrials.gov Identifier: NCT00855595
• Recruitment Status: Completed
• First Posted: March 4, 2009
• Results First Posted: August 29, 2012
• Last Update Posted: March 31, 2020
• Sponsor: LEO Pharma
• Collaborator: Bayer
• Information provided by (Responsible Party): LEO Pharma

Study Description

Brief Summary:

Subjects with moderate papulopustular rosacea will be treated either with azelaic acid 15% gel topically plus an anti-inflammatory dose of doxycyline (40mg) daily or with metronidazole 1% gel topically once daily plus an anti-inflammatory dose of doxycycline (40mg) over at total of twelve weeks to determine the rapidity of improvement, and the length of time to reach 25%, 50% and 75% clearing compared to baseline.

Condition or disease	Intervention/treatment	Phase
Papulopustular Rosacea	Drug: Azelaic acid (Finacea, BAY39-6251); Drug: Metronidazole (Metrogel); Drug: Doxycycline (Oracea)	Phase 4

Detailed Description:

The change in inflammatory lesion count will be assessed at each post-baseline visit by an analysis of variance model (ANOVA) with factors treatment and center, but not including treatment-by-center interaction.

Investigator's Global Assessment (IGA) of papulopustular rosacea (static score): 0 - Clear (Virtually no rosacea ie, no papules and/or pustules; no or residual erythema; no or mild to moderate degree of telangiectasia may be present); 1 - Minimal (Rare papules and/or pustules; residual to mild erythema; mild to moderate degree of telangiectasia may be present); 2 - Mild (Few papules and/or pustules; mild erythema; mild to moderate degree of telangiectasia may be present); 3 - Mild to moderate (Distinct number of papules and/or pustules; mild to moderate erythema; mild to moderate degree of telangiectasia may be present); 4 - Moderate (Pronounced number of papules and/or pustules; moderate erythema; mild to moderate degree of telangiectasia may be present); 5 - Moderate to severe (Many papules and/or pustules, occasionally with large inflamed lesions; moderate erythema; moderate degree of telangiectasia may be present); 6 - Severe (Numerous papules and/or pustules, occasionally with confluent areas of inflamed lesions; moderate or severe erythema; moderate or severe degree of telangiectasia may be present).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: An Exploratory, Multicenter, Investigator-blinded, Active-controlled Study to Investigate the Efficacy of Topical Azelaic Acid (AzA)15% Gel Twice Daily or Metronidazole Topical Gel 1% Once Daily, Plus Anti-inflammatory Dose Doxycycline (40mg) Once Daily in Subjects With Moderate Papulopustular Rosacea
• Study Start Date: February 2009
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Azelaic acid (Finacea, BAY39-6251) plus Doxycycline (Oracea); Participants received topical azelaic acid gel 15% twice daily and doxycycline 40 mg once daily for 12 weeks	Drug: Azelaic acid (Finacea, BAY39-6251); Participants received topical azelaic acid gel 15% twice daily for 12 weeks; Drug: Doxycycline (Oracea); Participants received systemic doxycycline 40 mg once daily for 12 week
Active Comparator: Metronidazole (Metrogel) plus Doxycycline (Oracea); Participants received topical metronidazole 1% gel once daily and doxycycline 40 mg once daily for 12 weeks	Drug: Metronidazole (Metrogel); Participants received topical metronidazole 1% gel once daily for 12 weeks; Drug: Doxycycline (Oracea); Participants received systemic doxycycline 40 mg once daily for 12 week

Outcome Measures

Primary Outcome Measures :

1. Nominal Change From Baseline in Inflammatory Lesion (IL) Count (Sum of Papules and Pustules) at Week 2 (LOCF: Last Observation Carried Forward) [ Time Frame: Baseline and Week 2 ]
   NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)

Secondary Outcome Measures :

1. Number of Inflammatory Lesions at Weeks 2, 4, 6, 8 and 12 (LOCF) [ Time Frame: Week 2, 4, 6, 8 and 12 ]
2. Nominal Change From Baseline in IL Count at Weeks 4, 6, 8 and 12 (LOCF) [ Time Frame: Baseline and Week 4, 6, 8 and 12 ]
   NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)
3. Percent Change From Baseline in IL Count at Weeks 2, 4, 6, 8 and 12 (LOCF) [ Time Frame: Baseline and Week 2, 4, 6, 8 and 12 ]
   NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)
4. Percentage of Participants With at Least a 25%, 50%, or 75% Improvement in Facial IL Counts From Baseline to Weeks 2, 4, 6, 8 and 12 (LOCF) [ Time Frame: Baseline and Weeks 2, 4, 6, 8 and 12 ]
5. Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at Weeks 2, 4, 6, 8 and 12 (LOCF) [ Time Frame: Weeks 2, 4, 6, 8 and 12 ]
   IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information) / Therapeutic success is defined as an IGA score of clear or minimal (0 or 1).
6. Percentage of Participants With IGA Based Patient Response at Weeks 2, 4, 6, 8 and 12 (LOCF) [ Time Frame: Weeks 2, 4, 6, 8 and 12 ]
   IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information) / Patient response is defined as an IGA score of clear, minimal, or mild (0, 1, or 2)
7. Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 2 [ Time Frame: At Week 2 ]
   IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information).
8. Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 4 [ Time Frame: At Week 4 ]
   IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information).
9. Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 6 [ Time Frame: At Week 6 ]
   IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information).
10. Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 8 [ Time Frame: At Week 8 ]
    IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information).
11. Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 12 [ Time Frame: At Week 12 ]
    IGA categories: 0 - Clear; 1 - Minimal; 2 - Mild; 3 - Mild to moderate; 4 - Moderate; 5 - Moderate to severe; 6 - Severe (refer to Detailed Description field in Protocol section for more information).
12. Investigator Rating of Overall Improvement at End of Study (Week 12) [ Time Frame: Week 12 ]
13. Patient Rating of Overall Improvement at End of Study (Week 12) [ Time Frame: Week 12 ]
14. Patient Opinion of Cosmetic Acceptability at End of Study (Week 12) [ Time Frame: Week 12 ]

Other Outcome Measures:

1. Patient Opinion of Local Tolerability [ Time Frame: Week 12 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

- Moderate papulopustular rosacea (IGA>4) with a minimum of 10 and no more than 50 inflammatory lesions and persistent erythema with or without telangiectasia

Exclusion Criteria:

• Sensitivity to any of the treatments used
• Co-existing conditions that would unfavorably influence the course of the disease
• Pregnant or lactating women
• Severe rosacea

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States, 35233

United States, Colorado

Denver, Colorado, United States, 80209

United States, Florida

West Palm Beach, Florida, United States, 33401

United States, Massachusetts

Boston, Massachusetts, United States, 02114-2517

United States, Michigan

Warren, Michigan, United States, 48088

United States, Minnesota

Fridley, Minnesota, United States, 55432

United States, Nevada

Henderson, Nevada, United States, 89052

United States, New Mexico

Albuquerque, New Mexico, United States, 87106

United States, New York

Stony Brook, New York, United States, 11790

United States, Ohio

Mason, Ohio, United States, 45040

United States, Oregon

Portland, Oregon, United States, 97223

United States, Texas

Austin, Texas, United States, 78759

Dallas, Texas, United States, 75246

Houston, Texas, United States, 77056

San Antonio, Texas, United States, 78229

United States, Utah

Salt Lake City, Utah, United States, 84124

United States, Virginia

Norfolk, Virginia, United States, 23507

Sponsors and Collaborators

LEO Pharma

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Publications of Results:

Del Rosso JQ, Bruce S, Jarratt M, Menter A, Staedtler G. Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea. J Drugs Dermatol. 2010 Jun;9(6):607-13.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT00855595
• Other Study ID Numbers: 14366; 1402604 ( Other Identifier: Intendis GmbH ); 256-0024 ( Other Identifier: Intendis GmbH )
• First Posted: March 4, 2009
• Results First Posted: August 29, 2012
• Last Update Posted: March 31, 2020
• Last Verified: January 2014

Keywords provided by LEO Pharma:

Rosacea

Additional relevant MeSH terms:

Rosacea; Skin Diseases; Metronidazole; Doxycycline; Azelaic acid; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Antineoplastic Agents; Dermatologic Agents