Evaluation of Rosacea-related Inflammatory Biochemical Markers in Adult Skin When Treated With Oracea® vs Placebo

Study Overview
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Brief Summary
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The objective of this study is to determine the clinical effects of doxycycline 40 mg (30 mg immediate release and 10 mg delayed release beads) capsules (Oracea®) as compared to placebo in the skin of adults with papulopustular rosacea and to identify a correlation, if any, with rosacea-related inflammatory markers.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Evaluation of Rosacea-related Inflammatory Biochemical Markers in the Skin of Adults With Papulopustular Rosacea Treated With Daily Doxycycline 40 mg (30 mg Immediate Release / 10 mg Delayed Release Beads) Capsules

Conditions
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Rosacea

Intervention / Treatment
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* Drug: Doxycycline
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female aged 18 to 70 years inclusive Subject with papulopustular rosacea (5 to 40 papules or pustules) Exclusion Criteria: Subject has any other active dermatological condition on face that may interfere with the conduct of the study Subject uses proton pump inhibitors for treatment of gastroesophageal reflux within 30 days prior to baseline visit or during the study Subject uses spironolactone within 30 days prior to baseline visit or during the study Subject requires chronic treatment (>14 days) with sulfa drugs, erythromycin, cephalosporins and quinolones within 30 days prior to baseline visit or during the study Subject has used tetracycline antibiotics within 30 days prior to baseline visit or during the study Subject has used penicillin antibiotics within 30 days prior to baseline visit or during the study Subject uses topical or oral dapsone Subject has had a change in hormonal therapy within 3 months of initiation of therapy or during the study Subject has used systemic immunosuppressants (e.g. corticosteroids, cyclosporine, imuran, biologics, mycophenolate mofetil) within 30 days prior to baseline visit. For subjects who have received treatment with biologics, treatment must have been discontinued within 90 days prior to baseline Subject has used any systemic therapy directed at improving rosacea, including antibiotics, within 30 days prior to baseline visit Subject has used systemic retinoids within 6 months of the baseline visit Subject takes niacin at a dosage of 500 mg or more per day Subject has used any topical rosacea therapy including topical antibiotics, topical retinoids, topical sodium sulfacetamide preparations, topical benzoyl peroxides, topical vasoconstricting agents (e.g., oxymetazoline) topical calcineurin inhibitors (e.g. tacrolimus, pimecrolimus) within 30 days prior to baseline visit Subject has been treated with another investigational drug or device within 30 days of baseline visit. For subjects who received experimental biologic treatment, treatment must have been discontinued within five half lives of the baseline visit. Subject has a known allergy to any of the components of the study products, and/or a known hypersensitivity to tetracyclines Subject is using a clinically significant concomitant drug (e.g., use of long term non-steroidal anti-inflammatory agents unless used only on a PRN basis less than 7 days per month) Subject has used vasodilators or an adrenergic blocking agent within 6 weeks of baseline visit (except subjects on stable dose for greater than 3 months) Subject has had laser or light therapy on the face within 3 months of the baseline visit Subject with active ocular rosacea and/or blepharitis/meibomianitis requiring systemic treatment by an ophthalmologist Subject with rhinophymatous rosacea Subject with a history of noncompliance with a treatment regimen Subject is at risk in terms of precautions, warnings, and contraindications (see package insert) Subject has previously failed to have improvement of rosacea with appropriate use of systemic tetracycline family of antibiotics Subjects with a recent history of alcohol and/or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oracea®<br>Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules | Drug: Doxycycline<br>* doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules, oral, one capsule daily in the morning<br>* Other names: Oracea®;|
| Active Comparator: placebo<br>placebo | Other: Placebo<br>* Placebo, oral, one capsule daily in the morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Inflammatory Lesion Counts | Mean change in inflammatory lesion counts from baseline to week 12 | baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | Mean change from baseline to week 12 in biochemical markers of rosacea and expression in skin samples. A biological marker is a substance used as an indicator of a biological state such as rosacea. Biochemical markers are serine protease activity and expression, metalloprotease activity and expression, and production of leucine leucine-37 [LL-37] peptide. | baseline to week 12 | 
| Investigator's Global Assessment (IGA) Scores at Week 12 | Number of participants in each category of the Investigator's Global Assessment (IGA) scores at week 12. Investigator's Global Assessment evaluates papules and pustules of rosacea on a scale from 0 - 4 (0 = Clear, 1 = Near Clear, 2 = Mild, 3 = Moderate and 4 = Severe) with 0 being best and 4 being worst. | Week 12 | 
| Change From Baseline in Clinician's Erythema Assessment (CEA) Scores | Mean change in Clinician's Erythema Assessment (CEA) from baseline to week 12. Clinician's Erythema Assessment evaluates erythema on a scale from 0 - 4 (0 = None, 1 = Mild, 2 = Moderate, 3 = Significant and 4 = Severe) with 0 being best and 4 being worst. | baseline to week 12 |