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

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

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.

Study Overview

• Status: Completed
• Conditions: Papulopustular Rosacea
• Intervention / Treatment: Drug: Azelaic acid (Finacea, BAY39-6251); Drug: Doxycycline (Oracea); Drug: Metronidazole (Metrogel)

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 Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
  • Colorado
    • Denver, Colorado, United States, 80209
  • Florida
    • West Palm Beach, Florida, United States, 33401
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2517
  • Michigan
    • Warren, Michigan, United States, 48088
  • Minnesota
    • Fridley, Minnesota, United States, 55432
  • Nevada
    • Henderson, Nevada, United States, 89052
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
  • New York
    • Stony Brook, New York, United States, 11790
  • Ohio
    • Mason, Ohio, United States, 45040
  • Oregon
    • Portland, Oregon, United States, 97223
  • Texas
    • Austin, Texas, United States, 78759
    • Dallas, Texas, United States, 75246
    • Houston, Texas, United States, 77056
    • San Antonio, Texas, United States, 78229
  • Utah
    • Salt Lake City, Utah, United States, 84124
  • Virginia
    • Norfolk, Virginia, United States, 23507

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: Doxycycline (Oracea); Participants received systemic doxycycline 40 mg once daily for 12 week; Drug: Metronidazole (Metrogel); Participants received topical metronidazole 1% gel once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Inflammatory Lesions at Weeks 2, 4, 6, 8 and 12 (LOCF)		Week 2, 4, 6, 8 and 12
Nominal Change From Baseline in IL Count at Weeks 4, 6, 8 and 12 (LOCF)	NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)	Baseline and Week 4, 6, 8 and 12
Percent Change From Baseline in IL Count at Weeks 2, 4, 6, 8 and 12 (LOCF)	NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)	Baseline and Week 2, 4, 6, 8 and 12
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)		Baseline and Weeks 2, 4, 6, 8 and 12
Percentage of Participants With Investigator's Global Assessment (IGA) Based Therapeutic Success at Weeks 2, 4, 6, 8 and 12 (LOCF)	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).	Weeks 2, 4, 6, 8 and 12
Percentage of Participants With IGA Based Patient Response at Weeks 2, 4, 6, 8 and 12 (LOCF)	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)	Weeks 2, 4, 6, 8 and 12
Percentage of Participants With Respective Disease Severity Measured by IGA Scores 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).	At Week 2
Percentage of Participants With Respective Disease Severity Measured by IGA Scores 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).	At Week 4
Percentage of Participants With Respective Disease Severity Measured by IGA Scores 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).	At Week 6
Percentage of Participants With Respective Disease Severity Measured by IGA Scores 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).	At Week 8
Percentage of Participants With Respective Disease Severity Measured by IGA Scores 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).	At Week 12
Investigator Rating of Overall Improvement at End of Study (Week 12)		Week 12
Patient Rating of Overall Improvement at End of Study (Week 12)		Week 12
Patient Opinion of Cosmetic Acceptability at End of Study (Week 12)		Week 12

Other Outcome Measures

Outcome Measure	Time Frame
Patient Opinion of Local Tolerability	Week 12

Collaborators and Investigators

• Sponsor: LEO Pharma
• Collaborators: Bayer

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: March 3, 2009
• First Submitted That Met QC Criteria: March 3, 2009
• First Posted (Estimate): March 4, 2009

Study Record Updates

• Last Update Posted (Actual): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 30, 2020
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Rosacea
• Additional Relevant MeSH Terms: Skin Diseases; Rosacea; Anti-Infective Agents; Antineoplastic Agents; Dermatologic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Metronidazole; Doxycycline; Azelaic acid
• Other Study ID Numbers: 14366; 1402604 (Other Identifier: Intendis GmbH); 256-0024 (Other Identifier: Intendis GmbH)