Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety

receive the brand tablet formulation of oral sarecycline (Seysara) once daily based on weight-based dosing as described in the approved product labeling for acne vulgaris (group A), or one tablet daily of Centrum Adult Multivitamin (group B) in a 3:1 ratio, respectively. The study duration was 12 weeks, with scheduled visits for screening, baseline, at week 4, at week 8, and at week 12 (end of study (EOS]). The study protocol was Institutional Review Board (IRB)-approved. All sites carried out the study in keeping with local legal and regulatory requirements, abided by principles defined in the recognized “Guideline for Good Clinical Practice”, and strictly followed ethical principles described in the current version of the Declaration of Helsinki.

Inclusion Criteria
The study required enrollment of adult subjects (≥18 years of age) of either gender. Females of child-bearing potential were required to have a negative urine pregnancy test before enrollment and had to agree to use an effective method of contraception throughout the study. Importantly, a sterile sexual partner was not considered as an adequate form of birth control for entry into the study. All enrolled subjects agreed to minimize recognized or known external factors that might trigger rosacea flare-ups, such as spicy foods, thermally hot foods/drinks, hot ambient environmental temperature, prolonged sun exposure, and alcoholic beverages. Any subject utilizing facial makeup agreed to use the same brands/types of make-up and usage frequency for a minimum period of 14 days prior to study entry and throughout the study. The following inclusion criteria for facial papulopustular rosacea were required at baseline in order to be considered for randomization into the study:

1. Moderate or severe rosacea based on Investigator Global Assessment rating (Table 1)
2. At least 15 and <50 facial papules and pustules; no more than 2 facial nodules
3. Presence of or history of facial erythema and/or flushing

Exclusion Criteria
Subjects were excluded from enrollment in the study for any of the following reasons:

1. Women who are pregnant, lactating, or planning to become pregnant during the study period.
2. Presence of any facial skin condition that would interfere with the diagnosis or assessment of rosacea, including excessive facial hair.
3. Moderate or severe rhinophyma, dense telangiectasia, or plaque-like facial edema.
4. History of hypersensitivity or allergy to all tetracyclines, or to any component of the formulation, history of C difficile-associated colitis, or history of intracranial hypertension (pseudotumor cerebi).
5. Severe erythema, dryness, scaling, pruritus, stinging/ burning, or edema.
6. Use within 6 months of oral retinoids or therapeutic vitamin A supplements of greater than 10,000 units/day (standard multivitamins are allowed).
7. Initiation of estrogens or oral contraceptives less than 3 months prior to baseline visit.
8. Use of systemic antibiotics with a known impact on the severity of facial rosacea and/or systemic corticosteroids within 1 month of baseline visit.
9. Use of topical agents including corticosteroids, antibiotics or rosacea medications, wax epilation or facial sauna/ spa/cosmetic treatments within 2 weeks of baseline visit.
10. Active bacterial folliculitis.
11. Exposure to potential rosacea trigger factors such as excessive, prolonged exposure to sunlight, or weather extremes.
12. Presence of conditions that may compromise subject ability to comply with study requirements such as excessive alcohol use and/or abuse of licit or illicit drugs.
13. Presence of any condition that in the opinion of the Investigator would interfere with study evaluations or optimal participation in the study.
14. Participation in an investigational drug study within 30 days prior to baseline visit.
15. Prior laser therapy, electrodessication, or phototherapy to the facial area within 180 days prior to baseline visit.

A primary duty of the investigator is discontinuation of study participation if desired by a subject at any point in time or if the health or well-being of a subject is threatened by continuation in the study. If premature study discontinuation occurs, the primary reason should be determined as best as possible.

At each visit, including screening, baseline, at week 4, at week 8, and at week 12 (EOS), informed consent and standard data collections were completed including inclusion/exclusion criteria, medical and surgical history, physical examination, vital signs, concomitant medications, tolerability and safety assessments, efficacy evaluations, and urine pregnancy testing (where applicable) following the Schedule of Study Assessments and Procedures mandated by the study protocol. Subject Global Assessment (SGA) ratings were also captured. Other than urinary pregnancy testing completed at all study visits in females of child-bearing potential, no other routine laboratory testing was completed during the study.

Efficacy Assessments
Primary Endpoints
The percent of subjects achieving clear or almost clear based on the protocol mandated IGA grading scale and the percent reduction of inflammatory lesions at week 12 are the primary endpoints. The IGA score was determined at each visit (Table 1).