Rosacea
Conditions
Brief summary
The purpose of this study is to assess relapse, efficacy and safety in subjects with rosacea during long-term treatment with either Oracea® or placebo, after an initial 12-week regimen of Oracea® and MetroGel® 1%.
Detailed description
Adult subjects with moderate to severe papulopustular rosacea will receive Oracea® and MetroGel® 1% once daily during phase 1 (baseline to week 12) of the study. Subjects will be eligible to enter phase 2 of the study based upon improvements in the Investigator's Global Assessment (IGA) score. During phase 2, subjects will receive either Oracea® or placebo once daily for up to an additional 40 weeks. Subjects who relapse during phase 2 will be discontinued from the study.
Interventions
DRUGDoxycycline
During phase 1 (baseline - week 12): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning During phase 1 (baseline - week 12) and phase 2 (week 12 - week 52): Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads), oral, one capsule daily in the morning
DRUGMetronidazole
During Phase 1: MetroGel 1% (metronidazole 1% gel), topical, apply a thin layer once daily to the affected area
DRUGPlacebo
During phase 2 (week 12 - week 52): placebo, oral, one capsule daily in the morning
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subject is male or female aged 18 to 80 years inclusive. * Subject with papulopustular rosacea (11 to 40 papules or pustules) and an IGA of moderate or severe. * For subjects using medications to treat a concurrent medical condition, type and dose must have been stable for at least 90 days prior to study entry.
Exclusion criteria
* Female subjects who are pregnant, nursing or planning a pregnancy during the study. * Subject has any other active dermatological condition on the face that may interfere with the conduct of the study. * Subject uses or has recently used any medication which may interfere with the absorption, distribution, or elimination of study medications, or may interfere with the assessments of efficacy or safety of the study medications. * Subject has a known allergy to any of the components of the study products, and/or a known hypersensitivity to tetracyclines or metronidazole.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period 2: Number of Subjects Who Relapsed | Period 2 (40 weeks) | Subjects who relapsed during phase 2 were discontinued. Relapse was defined as meeting any one of the following criteria: * A return to the baseline lesion count * A return to the baseline IGA score * The investigator determines that a change in rosacea treatment is warranted due to the subject's clinical condition. The numbers reported here are accumulative numbers for each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period 2: Investigator's Global Assessment Success | Period 2 (40 weeks) | The evaluator (investigator) assessed the severity of rosacea at baseline and each postbaseline visit using a 5 point Investigator's Global Assessment scale. Subjects scores were then dichotomized into success (clear or near clear score) or failure (mild, moderate, or severe score). |
| Period 2: Clinician's Erythema Assessment | Period 2 (40 Weeks) | The evaluator (investigator) assessed the severity of erythema at baseline and each postbaseline visit using a total erythema score. The erythema of 5 areas of the face (forehead, chin, nose, right cheek, left cheek) was scored using a 5 point Clinician's Erythema Assessment scale (0 = none, 1 = mild, 2 = moderate, 3 = significant, 4 = severe). The total of the 5 individual erythema scores scores was the total erythema score. |
| Period 2: Inflammatory Lesion Count | Period 2 (40 Weeks) | The evaluator (investigator or a designee) performed lesion counts at each postbaseline visit. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Period 1: Tolerability (Stinging/Burning) | Period 1 (12 Weeks) | Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole. |
| Period 1: Tolerability (Dryness) | Period 1 (12 Weeks) | Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole. |
| Period 1: Tolerability (Scaling) | Period 1 (12 Weeks) | Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole. |
Countries
United States
Participant flow
Pre-assignment details
Subjects were treated with doxycycline or placebo for 52 weeks (Period 2) after a 12 week treatment regimen of doxycycline and metronidazole (Period 1). Subjects who completed period 1 with clear/near clear IGA, or achieved at least a 2 grade IGA improvement were eligible for period 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Period 1: Oral Doxycycline and Topical Metronidazole Subjects will receive oral doxycycline and topical metronidazole during period 1 (12 weeks)
Oral Doxycycline and Topical Metronidazole: period 1, Oracea (doxycycline 40 mg USP (30 mg immediate release & 10 mg delayed release beads)), oral, one capsule daily in the morning and MetroGel 1% (metronidazole 1% gel), topical, apply a thin layer once daily to the affected area | 230 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Eligibility for Period 2, Randomization | Did not qualify | 42 | 0 | 0 |
| Eligibility for Period 2, Randomization | Qualified, opted out | 8 | 0 | 0 |
| Period 1: 12 Weeks | Adverse Event | 5 | 0 | 0 |
| Period 1: 12 Weeks | Lost to Follow-up | 22 | 0 | 0 |
| Period 1: 12 Weeks | Pregnancy | 1 | 0 | 0 |
| Period 1: 12 Weeks | Protocol Violation | 5 | 0 | 0 |
| Period 1: 12 Weeks | Withdrawal by Subject | 22 | 0 | 0 |
| Period 2: 40 Weeks | Adverse Event | 0 | 1 | 2 |
| Period 2: 40 Weeks | Lost to Follow-up | 0 | 8 | 6 |
| Period 2: 40 Weeks | Protocol Violation | 0 | 5 | 5 |
| Period 2: 40 Weeks | Relapsed | 0 | 9 | 18 |
| Period 2: 40 Weeks | Site closed | 0 | 6 | 5 |
| Period 2: 40 Weeks | Withdrawal by Subject | 0 | 9 | 11 |
Baseline characteristics
| Characteristic | Period 1: Oral Doxycycline and Topical Metronidazole |
|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| FItzpatrick Skin Type I | 16 participants |
| FItzpatrick Skin Type II | 93 participants |
| FItzpatrick Skin Type III | 64 participants |
| FItzpatrick Skin Type IV | 42 participants |
| FItzpatrick Skin Type V | 15 participants |
| FItzpatrick Skin Type VI | 0 participants |
| Height | 66.0 inches STANDARD_DEVIATION 3.8 |
| History of Rosacea | 4.4 years STANDARD_DEVIATION 7.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 217 Participants |
| Region of Enrollment United States | 230 participants |
| Sex: Female, Male Female | 164 Participants |
| Sex: Female, Male Male | 66 Participants |
| Skin Type Combination | 102 participants |
| Skin Type Dry | 40 participants |
| Skin Type Normal | 50 participants |
| Skin Type Oily | 38 participants |
| Weight | 180.2 pounds STANDARD_DEVIATION 45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 235 | 6 / 65 | 7 / 65 |
| serious Total, serious adverse events | 4 / 235 | 2 / 65 | 2 / 65 |
Outcome results
Primary
Period 2: Number of Subjects Who Relapsed
Subjects who relapsed during phase 2 were discontinued. Relapse was defined as meeting any one of the following criteria: * A return to the baseline lesion count * A return to the baseline IGA score * The investigator determines that a change in rosacea treatment is warranted due to the subject's clinical condition. The numbers reported here are accumulative numbers for each arm.
Time frame: Period 2 (40 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 12 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 24 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 4 | 4 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 28 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 16 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 32 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 8 | 8 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 36 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 20 | 9 participants |
| Oral Doxycycline | Period 2: Number of Subjects Who Relapsed | Week 40 | 9 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 20 | 16 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 8 | 14 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 40 | 18 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 12 | 16 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 16 | 16 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 4 | 10 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 24 | 17 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 28 | 18 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 32 | 18 participants |
| Placebo | Period 2: Number of Subjects Who Relapsed | Week 36 | 18 participants |
Secondary
Period 2: Clinician's Erythema Assessment
The evaluator (investigator) assessed the severity of erythema at baseline and each postbaseline visit using a total erythema score. The erythema of 5 areas of the face (forehead, chin, nose, right cheek, left cheek) was scored using a 5 point Clinician's Erythema Assessment scale (0 = none, 1 = mild, 2 = moderate, 3 = significant, 4 = severe). The total of the 5 individual erythema scores scores was the total erythema score.
Time frame: Period 2 (40 Weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 4 | 5.0 units on a scale | Standard Deviation 3.1 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 24 | 4.4 units on a scale | Standard Deviation 3.5 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 28 | 4.3 units on a scale | Standard Deviation 3.5 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 32 | 4.2 units on a scale | Standard Deviation 3.6 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 8 | 4.9 units on a scale | Standard Deviation 3.5 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 12 | 4.7 units on a scale | Standard Deviation 3.4 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 16 | 4.7 units on a scale | Standard Deviation 3.4 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 20 | 4.3 units on a scale | Standard Deviation 3.4 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 36 | 4.4 units on a scale | Standard Deviation 3.6 |
| Oral Doxycycline | Period 2: Clinician's Erythema Assessment | Week 40 | 4.4 units on a scale | Standard Deviation 3.5 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 16 | 5.2 units on a scale | Standard Deviation 3.8 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 12 | 5.3 units on a scale | Standard Deviation 4.3 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 20 | 5.5 units on a scale | Standard Deviation 3.8 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 8 | 5.8 units on a scale | Standard Deviation 3.9 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 24 | 5.3 units on a scale | Standard Deviation 3.8 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 36 | 5.3 units on a scale | Standard Deviation 3.8 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 28 | 5.3 units on a scale | Standard Deviation 3.8 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 40 | 5.3 units on a scale | Standard Deviation 3.9 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 32 | 5.3 units on a scale | Standard Deviation 3.9 |
| Placebo | Period 2: Clinician's Erythema Assessment | Week 4 | 5.6 units on a scale | Standard Deviation 3.8 |
Secondary
Period 2: Inflammatory Lesion Count
The evaluator (investigator or a designee) performed lesion counts at each postbaseline visit.
Time frame: Period 2 (40 Weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 24 | 2.2 lesions | Standard Deviation 2.7 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 8 | 3.1 lesions | Standard Deviation 4.1 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 28 | 2.2 lesions | Standard Deviation 2.8 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 12 | 3.0 lesions | Standard Deviation 4.2 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 32 | 2.2 lesions | Standard Deviation 3 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 16 | 2.4 lesions | Standard Deviation 4 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 36 | 2.5 lesions | Standard Deviation 3.1 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 20 | 2.1 lesions | Standard Deviation 2.2 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 40 | 2.1 lesions | Standard Deviation 2.6 |
| Oral Doxycycline | Period 2: Inflammatory Lesion Count | Week 4 | 2.8 lesions | Standard Deviation 4.5 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 40 | 1.6 lesions | Standard Deviation 1.9 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 4 | 5.8 lesions | Standard Deviation 8.7 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 12 | 1.9 lesions | Standard Deviation 2.7 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 16 | 2.3 lesions | Standard Deviation 2.6 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 20 | 2.6 lesions | Standard Deviation 3.1 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 24 | 2.9 lesions | Standard Deviation 3.9 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 28 | 2.9 lesions | Standard Deviation 4 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 32 | 2.4 lesions | Standard Deviation 3.3 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 36 | 2.2 lesions | Standard Deviation 3 |
| Placebo | Period 2: Inflammatory Lesion Count | Week 8 | 4.3 lesions | Standard Deviation 6 |
Secondary
Period 2: Investigator's Global Assessment Success
The evaluator (investigator) assessed the severity of rosacea at baseline and each postbaseline visit using a 5 point Investigator's Global Assessment scale. Subjects scores were then dichotomized into success (clear or near clear score) or failure (mild, moderate, or severe score).
Time frame: Period 2 (40 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 32 | 39 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 4 | 44 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 8 | 36 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 12 | 33 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 16 | 38 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 20 | 35 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 24 | 36 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 28 | 39 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 36 | 40 participants |
| Oral Doxycycline | Period 2: Investigator's Global Assessment Success | Week 40 | 41 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 16 | 34 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 32 | 34 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 40 | 33 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 36 | 33 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 4 | 38 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 20 | 33 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 8 | 33 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 28 | 35 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 12 | 37 participants |
| Placebo | Period 2: Investigator's Global Assessment Success | Week 24 | 32 participants |
Other Pre-specified
Period 1: Tolerability (Dryness)
Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.
Time frame: Period 1 (12 Weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Doxycycline | Period 1: Tolerability (Dryness) | Severe | 10 participants |
| Oral Doxycycline | Period 1: Tolerability (Dryness) | Mild | 89 participants |
| Oral Doxycycline | Period 1: Tolerability (Dryness) | Missing | 0 participants |
| Oral Doxycycline | Period 1: Tolerability (Dryness) | Moderate | 60 participants |
| Oral Doxycycline | Period 1: Tolerability (Dryness) | None | 76 participants |
| Placebo | Period 1: Tolerability (Dryness) | Moderate | 32 participants |
| Placebo | Period 1: Tolerability (Dryness) | Severe | 2 participants |
| Placebo | Period 1: Tolerability (Dryness) | Missing | 17 participants |
| Placebo | Period 1: Tolerability (Dryness) | Mild | 78 participants |
| Placebo | Period 1: Tolerability (Dryness) | None | 106 participants |
| Week 8 | Period 1: Tolerability (Dryness) | Moderate | 13 participants |
| Week 8 | Period 1: Tolerability (Dryness) | None | 120 participants |
| Week 8 | Period 1: Tolerability (Dryness) | Mild | 61 participants |
| Week 8 | Period 1: Tolerability (Dryness) | Severe | 0 participants |
| Week 8 | Period 1: Tolerability (Dryness) | Missing | 41 participants |
| Week 12 | Period 1: Tolerability (Dryness) | Severe | 0 participants |
| Week 12 | Period 1: Tolerability (Dryness) | Mild | 37 participants |
| Week 12 | Period 1: Tolerability (Dryness) | None | 125 participants |
| Week 12 | Period 1: Tolerability (Dryness) | Moderate | 6 participants |
| Week 12 | Period 1: Tolerability (Dryness) | Missing | 67 participants |
Other Pre-specified
Period 1: Tolerability (Scaling)
Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.
Time frame: Period 1 (12 Weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Doxycycline | Period 1: Tolerability (Scaling) | Moderate | 44 participants |
| Oral Doxycycline | Period 1: Tolerability (Scaling) | Missing | 0 participants |
| Oral Doxycycline | Period 1: Tolerability (Scaling) | Severe | 3 participants |
| Oral Doxycycline | Period 1: Tolerability (Scaling) | None | 103 participants |
| Oral Doxycycline | Period 1: Tolerability (Scaling) | Mild | 85 participants |
| Placebo | Period 1: Tolerability (Scaling) | None | 136 participants |
| Placebo | Period 1: Tolerability (Scaling) | Mild | 58 participants |
| Placebo | Period 1: Tolerability (Scaling) | Severe | 0 participants |
| Placebo | Period 1: Tolerability (Scaling) | Missing | 17 participants |
| Placebo | Period 1: Tolerability (Scaling) | Moderate | 24 participants |
| Week 8 | Period 1: Tolerability (Scaling) | None | 139 participants |
| Week 8 | Period 1: Tolerability (Scaling) | Mild | 44 participants |
| Week 8 | Period 1: Tolerability (Scaling) | Moderate | 11 participants |
| Week 8 | Period 1: Tolerability (Scaling) | Severe | 0 participants |
| Week 8 | Period 1: Tolerability (Scaling) | Missing | 41 participants |
| Week 12 | Period 1: Tolerability (Scaling) | Severe | 0 participants |
| Week 12 | Period 1: Tolerability (Scaling) | Mild | 23 participants |
| Week 12 | Period 1: Tolerability (Scaling) | None | 143 participants |
| Week 12 | Period 1: Tolerability (Scaling) | Moderate | 2 participants |
| Week 12 | Period 1: Tolerability (Scaling) | Missing | 67 participants |
Other Pre-specified
Period 1: Tolerability (Stinging/Burning)
Scaling, dryness, and stinging/burning were graded at baseline and weeks 4, 8, and 12 for subjects taking oral doxycycline and topical metronidazole.
Time frame: Period 1 (12 Weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Doxycycline | Period 1: Tolerability (Stinging/Burning) | None | 90 participants |
| Oral Doxycycline | Period 1: Tolerability (Stinging/Burning) | Severe | 14 participants |
| Oral Doxycycline | Period 1: Tolerability (Stinging/Burning) | Moderate | 60 participants |
| Oral Doxycycline | Period 1: Tolerability (Stinging/Burning) | Missing | 0 participants |
| Oral Doxycycline | Period 1: Tolerability (Stinging/Burning) | Mild | 71 participants |
| Placebo | Period 1: Tolerability (Stinging/Burning) | Moderate | 31 participants |
| Placebo | Period 1: Tolerability (Stinging/Burning) | None | 135 participants |
| Placebo | Period 1: Tolerability (Stinging/Burning) | Mild | 51 participants |
| Placebo | Period 1: Tolerability (Stinging/Burning) | Severe | 1 participants |
| Placebo | Period 1: Tolerability (Stinging/Burning) | Missing | 17 participants |
| Week 8 | Period 1: Tolerability (Stinging/Burning) | Severe | 0 participants |
| Week 8 | Period 1: Tolerability (Stinging/Burning) | Mild | 44 participants |
| Week 8 | Period 1: Tolerability (Stinging/Burning) | Moderate | 11 participants |
| Week 8 | Period 1: Tolerability (Stinging/Burning) | Missing | 41 participants |
| Week 8 | Period 1: Tolerability (Stinging/Burning) | None | 139 participants |
| Week 12 | Period 1: Tolerability (Stinging/Burning) | None | 143 participants |
| Week 12 | Period 1: Tolerability (Stinging/Burning) | Missing | 67 participants |
| Week 12 | Period 1: Tolerability (Stinging/Burning) | Severe | 0 participants |
| Week 12 | Period 1: Tolerability (Stinging/Burning) | Mild | 19 participants |
| Week 12 | Period 1: Tolerability (Stinging/Burning) | Moderate | 6 participants |