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

Phase 4

Completed

• Conditions: Papulopustular Rosacea
• Interventions: Drug: Azelaic acid (Finacea, BAY39-6251); Drug: Metronidazole (Metrogel); Drug: Doxycycline (Oracea)

• Registration Number: NCT00855595
• Lead Sponsor: LEO Pharma

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.

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 Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-03-03
• Study First Submitted QC: 2009-03-03
• Study First Posted: 2009-03-04
• Primary Completion: 2009-04
• Study Completion: 2009-07
• Results First Submitted: 2012-07-25
• Results First Submitted QC: 2012-07-25
• Results First Posted: 2012-08-29
• Status Verified: 2014-01
• Last Update Submitted: 2020-03-30
• Last Update Posted: 2020-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 207

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azelaic acid (Finacea, BAY39-6251) plus Doxycycline (Oracea)	Azelaic acid (Finacea, BAY39-6251)	Participants received topical azelaic acid gel 15% twice daily and doxycycline 40 mg once daily for 12 weeks
Azelaic acid (Finacea, BAY39-6251) plus Doxycycline (Oracea)	Doxycycline (Oracea)	Participants received topical azelaic acid gel 15% twice daily and doxycycline 40 mg once daily for 12 weeks
Metronidazole (Metrogel) plus Doxycycline (Oracea)	Metronidazole (Metrogel)	Participants received topical metronidazole 1% gel once daily and doxycycline 40 mg once daily for 12 weeks
Metronidazole (Metrogel) plus Doxycycline (Oracea)	Doxycycline (Oracea)	Participants received topical metronidazole 1% gel once daily and doxycycline 40 mg once daily for 12 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Patient Rating of Overall Improvement at End of Study (Week 12)	Week 12
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)	Baseline and Week 4, 6, 8 and 12	NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)
Percent Change From Baseline in IL Count at Weeks 2, 4, 6, 8 and 12 (LOCF)	Baseline and Week 2, 4, 6, 8 and 12	NOTE: Negative mean values represent an improvement (decrease of inflammatory lesions)
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)	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).
Percentage of Participants With IGA Based Patient Response at Weeks 2, 4, 6, 8 and 12 (LOCF)	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)
Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 2	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).
Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 4	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).
Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 6	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).
Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 8	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).
Percentage of Participants With Respective Disease Severity Measured by IGA Scores at Week 12	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).
Investigator 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