Rosacea
Conditions
Brief summary
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.
Interventions
DRUGDoxycycline
doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules, oral, one capsule daily in the morning
OTHERPlacebo
Placebo, oral, one capsule daily in the morning
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Inflammatory Lesion Counts | baseline to week 12 | Mean change in inflammatory lesion counts from baseline to week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | 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. |
| Investigator's Global Assessment (IGA) Scores at Week 12 | 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. |
| Change From Baseline in Clinician's Erythema Assessment (CEA) Scores | baseline to week 12 | 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. |
Countries
United States
Participant flow
Recruitment details
First subject enrolled 9 May 2011, last subject last visit 2 July 2012
Participants by arm
| Arm | Count |
|---|---|
| Oracea® Doxycycline 40 mg (30 mg immediate release / 10 mg delayed release beads) Capsules | 84 |
| Placebo placebo | 86 |
| Total | 170 |
Baseline characteristics
| Characteristic | Oracea® | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 11.4 | 48.7 years STANDARD_DEVIATION 10.8 | 49.1 years STANDARD_DEVIATION 11.1 |
| Region of Enrollment United States | 84 participants | 86 participants | 170 participants |
| Sex: Female, Male Female | 61 Participants | 60 Participants | 121 Participants |
| Sex: Female, Male Male | 23 Participants | 26 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 84 | 6 / 86 |
| serious Total, serious adverse events | 2 / 84 | 0 / 86 |
Outcome results
Primary
Change From Baseline in Inflammatory Lesion Counts
Mean change in inflammatory lesion counts from baseline to week 12
Time frame: baseline to week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oracea® | Change From Baseline in Inflammatory Lesion Counts | -4.3 inflammatory lesions | Standard Deviation 7.9 |
| Placebo | Change From Baseline in Inflammatory Lesion Counts | -3.2 inflammatory lesions | Standard Deviation 8.6 |
Secondary
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.
Time frame: baseline to week 12
Population: Treatment success was defined as all subjects from either treatment group with a score of clear or near clear on the Investigator's Global Assessment (IGA) scale. Treatment failure was defined as all subjects from either treatment group with a score of mild, moderate, or severe on the IGA scale.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oracea® | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | Cathelicidin | -0.0931 micr grams protein | Standard Deviation 0.5491 |
| Oracea® | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | KLK5 | -0.0034 micr grams protein | Standard Deviation 0.011 |
| Oracea® | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | MMP9 | -0.0017 micr grams protein | Standard Deviation 0.01 |
| Oracea® | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | Total Protease | -22351.6 micr grams protein | Standard Deviation 102888.2 |
| Placebo | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | Total Protease | -22540.9 micr grams protein | Standard Deviation 66146.2 |
| Placebo | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | Cathelicidin | -0.0379 micr grams protein | Standard Deviation 0.1545 |
| Placebo | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | MMP9 | -0.0021 micr grams protein | Standard Deviation 0.0233 |
| Placebo | Change From Baseline in Biochemical Markers of Rosacea From Tape Stripping and/or Skin Biopsy From Baseline to Week 12 | KLK5 | -0.0049 micr grams protein | Standard Deviation 0.0146 |
Secondary
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.
Time frame: baseline to week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oracea® | Change From Baseline in Clinician's Erythema Assessment (CEA) Scores | -1.0 units on a scale | Standard Deviation 2.9 |
| Placebo | Change From Baseline in Clinician's Erythema Assessment (CEA) Scores | -0.8 units on a scale | Standard Deviation 3.1 |
Secondary
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.
Time frame: Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oracea® | Investigator's Global Assessment (IGA) Scores at Week 12 | Mild | 35 participants |
| Oracea® | Investigator's Global Assessment (IGA) Scores at Week 12 | Moderate | 12 participants |
| Oracea® | Investigator's Global Assessment (IGA) Scores at Week 12 | Severe | 6 participants |
| Oracea® | Investigator's Global Assessment (IGA) Scores at Week 12 | Clear | 8 participants |
| Oracea® | Investigator's Global Assessment (IGA) Scores at Week 12 | Near Clear | 23 participants |
| Placebo | Investigator's Global Assessment (IGA) Scores at Week 12 | Near Clear | 18 participants |
| Placebo | Investigator's Global Assessment (IGA) Scores at Week 12 | Clear | 2 participants |
| Placebo | Investigator's Global Assessment (IGA) Scores at Week 12 | Moderate | 20 participants |
| Placebo | Investigator's Global Assessment (IGA) Scores at Week 12 | Mild | 31 participants |
| Placebo | Investigator's Global Assessment (IGA) Scores at Week 12 | Severe | 15 participants |